Hematology Times

Photo by Jorge Ferreira

The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.

Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.

The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.

Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).

At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.

Artemis Therapeutics, Inc. has not yet released safety data from this trial.

Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Jorge Ferreira

The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.

Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.

The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.

Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).

At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.

Artemis Therapeutics, Inc. has not yet released safety data from this trial.

Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Jorge Ferreira

The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.

Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.

The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.

Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).

At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.

Artemis Therapeutics, Inc. has not yet released safety data from this trial.

Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.

Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.

“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.

The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.

In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.

Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.

“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.

The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.

In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

Image by Lance Liotta

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.

Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.

“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.

The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.

In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to ACH-4471 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

And the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products has recommended the drug receive orphan status for the same indication in the European Economic Area.

ACH-4471 is a factor D inhibitor being developed by Achillion Pharmaceuticals, Inc.

In April, the company announced the initiation of a phase 2, three-month, dose-ranging trial with ACH-4471 for patients with untreated PNH (NCT03053102).

The primary objective of the trial is to assess the change from baseline in serum lactate dehydrogenase (LDH) levels. Secondary endpoints include changes in hemoglobin, PNH red blood cells, fatigue score (FACIT scale), changes in levels of complement pathway biomarkers such as Bb and factor D, pharmacokinetics, and safety.

The protocol allows for intra-patient dose-escalation. Patients initially receive 100 mg or 150 mg of ACH-4471 three times daily, and doses may be increased during the treatment period.

After patients complete 3 months of treatment and investigators have assessed safety and clinical benefit, patients may be enrolled in the long-term extension trial (NCT03181633).

To date, 200 mg three times daily has been the highest dose of ACH-4471 administered. And Achillion has collected data on 4 patients.

Two of the patients have completed the 3-month trial and entered the long-term extension trial. One patient continues to receive dosing in the 3-month trial, and the fourth patient voluntarily withdrew from the trial on day 41 for reasons unrelated to safety.

Thus far, ACH-4471 has produced clinically meaningful complement inhibition and demonstrated a favorable tolerability profile, with no reports of clinically meaningful increases in liver enzymes. ACH-4471 has improved LDH, hemoglobin, fatigue score, and other measures of response, including PNH clone size.

FDA’s orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

EMA’s orphan designation

The EMA’s orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. It also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to ACH-4471 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

And the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products has recommended the drug receive orphan status for the same indication in the European Economic Area.

ACH-4471 is a factor D inhibitor being developed by Achillion Pharmaceuticals, Inc.

In April, the company announced the initiation of a phase 2, three-month, dose-ranging trial with ACH-4471 for patients with untreated PNH (NCT03053102).

The primary objective of the trial is to assess the change from baseline in serum lactate dehydrogenase (LDH) levels. Secondary endpoints include changes in hemoglobin, PNH red blood cells, fatigue score (FACIT scale), changes in levels of complement pathway biomarkers such as Bb and factor D, pharmacokinetics, and safety.

The protocol allows for intra-patient dose-escalation. Patients initially receive 100 mg or 150 mg of ACH-4471 three times daily, and doses may be increased during the treatment period.

After patients complete 3 months of treatment and investigators have assessed safety and clinical benefit, patients may be enrolled in the long-term extension trial (NCT03181633).

To date, 200 mg three times daily has been the highest dose of ACH-4471 administered. And Achillion has collected data on 4 patients.

Two of the patients have completed the 3-month trial and entered the long-term extension trial. One patient continues to receive dosing in the 3-month trial, and the fourth patient voluntarily withdrew from the trial on day 41 for reasons unrelated to safety.

Thus far, ACH-4471 has produced clinically meaningful complement inhibition and demonstrated a favorable tolerability profile, with no reports of clinically meaningful increases in liver enzymes. ACH-4471 has improved LDH, hemoglobin, fatigue score, and other measures of response, including PNH clone size.

FDA’s orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

EMA’s orphan designation

The EMA’s orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. It also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to ACH-4471 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

And the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products has recommended the drug receive orphan status for the same indication in the European Economic Area.

ACH-4471 is a factor D inhibitor being developed by Achillion Pharmaceuticals, Inc.

In April, the company announced the initiation of a phase 2, three-month, dose-ranging trial with ACH-4471 for patients with untreated PNH (NCT03053102).

The primary objective of the trial is to assess the change from baseline in serum lactate dehydrogenase (LDH) levels. Secondary endpoints include changes in hemoglobin, PNH red blood cells, fatigue score (FACIT scale), changes in levels of complement pathway biomarkers such as Bb and factor D, pharmacokinetics, and safety.

The protocol allows for intra-patient dose-escalation. Patients initially receive 100 mg or 150 mg of ACH-4471 three times daily, and doses may be increased during the treatment period.

After patients complete 3 months of treatment and investigators have assessed safety and clinical benefit, patients may be enrolled in the long-term extension trial (NCT03181633).

To date, 200 mg three times daily has been the highest dose of ACH-4471 administered. And Achillion has collected data on 4 patients.

Two of the patients have completed the 3-month trial and entered the long-term extension trial. One patient continues to receive dosing in the 3-month trial, and the fourth patient voluntarily withdrew from the trial on day 41 for reasons unrelated to safety.

Thus far, ACH-4471 has produced clinically meaningful complement inhibition and demonstrated a favorable tolerability profile, with no reports of clinically meaningful increases in liver enzymes. ACH-4471 has improved LDH, hemoglobin, fatigue score, and other measures of response, including PNH clone size.

FDA’s orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

EMA’s orphan designation

The EMA’s orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. It also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission.

Photo courtesy of NIH

NEW YORK, NY—Speakers faced off over the issue of minimal residual disease (MRD) testing in multiple myeloma (MM) at Lymphoma & Myeloma 2017.

Ola Landgren, MD, PhD, of Weill Cornell Medicine in New York, New York, said, “it’s really a necessary and logical step forward to look at MRD.”

On the other hand, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, took the clinicians’ perspective and suggested that, at this point, “we’re not yet ready to apply it to everyday practice.”

“[P]atients who have a complete response (CR) and are MRD negative have longer progression-free survival (PFS),” Dr Landgren pointed out, “and there are indications that their overall survival (OS) is better than in those patients who are just CR and MRD positive.”

“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena,” Dr Richardson contended. “The question for me, as a clinician, in my clinic, is ‘Do I apply it to everyday practice?’ And I would simply suggest to you, at this point, we’re not ready for that.”

Yes—MRD is ready for prime time

Dr Landgren based his argument on 2 meta-analyses published in 2016 and 2017 that outline the importance of MRD status in newly diagnosed MM patients.

The first analysis (Landgren et al 2016) showed that MRD negativity was associated with better PFS (hazard ratio [HR]=0.35] and OS (HR=0.48) than MRD positivity.

“So using more simple language,” Dr Landgren said, “this means that MRD negativity reduces the risk of progression by 65%, and it also reduces the risk of dying by 52%.”

The second analysis (Munshi et al 2017) also associated MRD-negative status with superior survival outcomes for both PFS (HR=0.41) and OS (HR=0.57).

As further confirmation of the importance of MRD status, the International Myeloma Working Group last year published response definitions that include MRD negativity at a sensitivity of 1 in 10⁵ cells or higher as the deepest level of treatment response in MM.

Dr Landgren drew on additional studies to support routine MRD testing in patient care.

The IFM Study Group found that, in newly diagnosed patients treated with lenalidomide, bortezomib, and dexamethasone followed by 1 year of lenalidomide maintenance, patients who received a subsequent transplant achieved superior outcomes compared to non-transplanted patients, in terms of CR (58% vs 46%) and 3-year PFS (61% vs 48%).

However, in patients who were MRD negative in both arms, the PFS rates were very similar, Dr Landgren said. And in terms of 3-year OS, there was no difference, at 88% in both arms.

The experience with daratumumab in relapsed/refractory patients exhibited a similar pattern.

The phase 3 POLLUX trial first showed that adding daratumumab to lenalidomide and dexamethasone was superior to lenalidomide and dexamethasone only, with a PFS at 18 months of 78% and 52%, respectively. This amounted to a 63% reduction in the risk of disease progression.

Investigators then took one more step forward, Dr Landgren said, and looked at MRD.

At a sensitivity of 10^-5, almost 25% of patients on the 3-drug regimen were MRD negative, “which is kind of amazing,” Dr Landgren said. “This is a very big step forward.”

“If you break down the results by MRD status, which is not the primary endpoint of the study, you see very similar patterns for PFS for MRD negative patients in each of the 2 arms,” he continued.

This raises the question of whether attaining MRD negativity is more important than the treatment modality.

MRD negativity has implications for speeding drug approvals, developing more sensitive assays, and future treatment management, Dr Landgren said.

No—MRD is not ready for prime time

Dr Richardson acknowledged that MRD assessment is important. However, he pointed out a number of caveats regarding how MRD assessment would be applied in clinical practice to support his position.

“I’d simply suggest to you that, in day-to-day practice, the definition [of MRD] is somewhat fluid,” he said. “And it varies, obviously, between diseases and technology used.”

For most malignancies, Dr Richardson said, 10⁹ to 10¹⁰ malignant cells are undetectable with conventional methods. These may or may not lead to a full clinical relapse within months or even years.

Using a sensitive technique to determine the presence of MRD could permit analysis of treatments that induce a greater depth of response or identify patients at risk of early relapse who need further treatment.

Dr Richardson enumerated hematologic malignancies that utilize MRD as secondary endpoints—acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

In chronic myeloid leukemia, MRD is used as a primary endpoint that dictates practice.

“And I would applaud the field in that area because, obviously, molecular response accepted as an endpoint by FDA for second-generation TKIs has been a bedrock of that approval process, and it now applies in clinical practice,” Dr Richardson said.

“Obviously, that’s where we’d like to be, but I’d suggest to you, just again, with a certain amount of moderation and a certain amount of caution, that we may not be quite there yet.”

Dr Richardson suggested that MRD assessment in MM is less advanced than in leukemia and lymphoma.

“[W]e are currently at the point where MRD assessments are clearly secondary endpoints, an important research tool,” he said.

Some “remarkable combination therapies,” he added, have abrogated some of the “extraordinary genetic complexity” in MM.

“The critical point here, though, is that, while we’re more successful in terms of these triplets and quadruplets and now with the introduction of monoclonal antibodies and similar approaches, we’re able to throw a bigger net around the disease,” Dr Richardson said.

“We’re not able to eradicate it completely, and cure remains, in myeloma, frankly, evasive. And I think that’s a critical point.”

Dr Richardson reviewed various strategies for molecular response monitoring, from flow cytometry to polymerase chain reaction and next-generation sequencing, noting that there is variance in applicability and sensitivity.

For example, the limits of detection among 91 labs ranged from 0.10% to 0.001%.

Dr Richardson returned to the “very robust” meta-analysis by Munshi and colleagues discussed by Dr Landgren.

While the authors’ analysis demonstrated that MRD is predictive of both longer PFS and OS, they concluded that the evidence supported MRD as an endpoint and research tool in clinical trials.

“So I would humbly suggest perhaps it’s not ready for clinical prime time yet,” Dr Richardson said.

He also referred to the IFM Study Group trial described by Dr Landgren, calling it a “critical forward effort.”

“[W]hat’s so interesting is that there was no difference in overall survival,” Dr Richardson said. “Now, that’s a very important point as we soberly look at these data and judge what they mean for each patient.”

And so Dr Richardson stood by his assessment that MRD is not yet a standard of care but may be one day. 

Photo courtesy of NIH

NEW YORK, NY—Speakers faced off over the issue of minimal residual disease (MRD) testing in multiple myeloma (MM) at Lymphoma & Myeloma 2017.

Ola Landgren, MD, PhD, of Weill Cornell Medicine in New York, New York, said, “it’s really a necessary and logical step forward to look at MRD.”

On the other hand, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, took the clinicians’ perspective and suggested that, at this point, “we’re not yet ready to apply it to everyday practice.”

“[P]atients who have a complete response (CR) and are MRD negative have longer progression-free survival (PFS),” Dr Landgren pointed out, “and there are indications that their overall survival (OS) is better than in those patients who are just CR and MRD positive.”

“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena,” Dr Richardson contended. “The question for me, as a clinician, in my clinic, is ‘Do I apply it to everyday practice?’ And I would simply suggest to you, at this point, we’re not ready for that.”

Yes—MRD is ready for prime time

Dr Landgren based his argument on 2 meta-analyses published in 2016 and 2017 that outline the importance of MRD status in newly diagnosed MM patients.

The first analysis (Landgren et al 2016) showed that MRD negativity was associated with better PFS (hazard ratio [HR]=0.35] and OS (HR=0.48) than MRD positivity.

“So using more simple language,” Dr Landgren said, “this means that MRD negativity reduces the risk of progression by 65%, and it also reduces the risk of dying by 52%.”

The second analysis (Munshi et al 2017) also associated MRD-negative status with superior survival outcomes for both PFS (HR=0.41) and OS (HR=0.57).

As further confirmation of the importance of MRD status, the International Myeloma Working Group last year published response definitions that include MRD negativity at a sensitivity of 1 in 10⁵ cells or higher as the deepest level of treatment response in MM.

Dr Landgren drew on additional studies to support routine MRD testing in patient care.

The IFM Study Group found that, in newly diagnosed patients treated with lenalidomide, bortezomib, and dexamethasone followed by 1 year of lenalidomide maintenance, patients who received a subsequent transplant achieved superior outcomes compared to non-transplanted patients, in terms of CR (58% vs 46%) and 3-year PFS (61% vs 48%).

However, in patients who were MRD negative in both arms, the PFS rates were very similar, Dr Landgren said. And in terms of 3-year OS, there was no difference, at 88% in both arms.

The experience with daratumumab in relapsed/refractory patients exhibited a similar pattern.

The phase 3 POLLUX trial first showed that adding daratumumab to lenalidomide and dexamethasone was superior to lenalidomide and dexamethasone only, with a PFS at 18 months of 78% and 52%, respectively. This amounted to a 63% reduction in the risk of disease progression.

Investigators then took one more step forward, Dr Landgren said, and looked at MRD.

At a sensitivity of 10^-5, almost 25% of patients on the 3-drug regimen were MRD negative, “which is kind of amazing,” Dr Landgren said. “This is a very big step forward.”

“If you break down the results by MRD status, which is not the primary endpoint of the study, you see very similar patterns for PFS for MRD negative patients in each of the 2 arms,” he continued.

This raises the question of whether attaining MRD negativity is more important than the treatment modality.

MRD negativity has implications for speeding drug approvals, developing more sensitive assays, and future treatment management, Dr Landgren said.

No—MRD is not ready for prime time

Dr Richardson acknowledged that MRD assessment is important. However, he pointed out a number of caveats regarding how MRD assessment would be applied in clinical practice to support his position.

“I’d simply suggest to you that, in day-to-day practice, the definition [of MRD] is somewhat fluid,” he said. “And it varies, obviously, between diseases and technology used.”

For most malignancies, Dr Richardson said, 10⁹ to 10¹⁰ malignant cells are undetectable with conventional methods. These may or may not lead to a full clinical relapse within months or even years.

Using a sensitive technique to determine the presence of MRD could permit analysis of treatments that induce a greater depth of response or identify patients at risk of early relapse who need further treatment.

Dr Richardson enumerated hematologic malignancies that utilize MRD as secondary endpoints—acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

In chronic myeloid leukemia, MRD is used as a primary endpoint that dictates practice.

“And I would applaud the field in that area because, obviously, molecular response accepted as an endpoint by FDA for second-generation TKIs has been a bedrock of that approval process, and it now applies in clinical practice,” Dr Richardson said.

“Obviously, that’s where we’d like to be, but I’d suggest to you, just again, with a certain amount of moderation and a certain amount of caution, that we may not be quite there yet.”

Dr Richardson suggested that MRD assessment in MM is less advanced than in leukemia and lymphoma.

“[W]e are currently at the point where MRD assessments are clearly secondary endpoints, an important research tool,” he said.

Some “remarkable combination therapies,” he added, have abrogated some of the “extraordinary genetic complexity” in MM.

“The critical point here, though, is that, while we’re more successful in terms of these triplets and quadruplets and now with the introduction of monoclonal antibodies and similar approaches, we’re able to throw a bigger net around the disease,” Dr Richardson said.

“We’re not able to eradicate it completely, and cure remains, in myeloma, frankly, evasive. And I think that’s a critical point.”

Dr Richardson reviewed various strategies for molecular response monitoring, from flow cytometry to polymerase chain reaction and next-generation sequencing, noting that there is variance in applicability and sensitivity.

For example, the limits of detection among 91 labs ranged from 0.10% to 0.001%.

Dr Richardson returned to the “very robust” meta-analysis by Munshi and colleagues discussed by Dr Landgren.

While the authors’ analysis demonstrated that MRD is predictive of both longer PFS and OS, they concluded that the evidence supported MRD as an endpoint and research tool in clinical trials.

“So I would humbly suggest perhaps it’s not ready for clinical prime time yet,” Dr Richardson said.

He also referred to the IFM Study Group trial described by Dr Landgren, calling it a “critical forward effort.”

“[W]hat’s so interesting is that there was no difference in overall survival,” Dr Richardson said. “Now, that’s a very important point as we soberly look at these data and judge what they mean for each patient.”

And so Dr Richardson stood by his assessment that MRD is not yet a standard of care but may be one day. 

Photo courtesy of NIH

NEW YORK, NY—Speakers faced off over the issue of minimal residual disease (MRD) testing in multiple myeloma (MM) at Lymphoma & Myeloma 2017.

Ola Landgren, MD, PhD, of Weill Cornell Medicine in New York, New York, said, “it’s really a necessary and logical step forward to look at MRD.”

On the other hand, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, took the clinicians’ perspective and suggested that, at this point, “we’re not yet ready to apply it to everyday practice.”

“[P]atients who have a complete response (CR) and are MRD negative have longer progression-free survival (PFS),” Dr Landgren pointed out, “and there are indications that their overall survival (OS) is better than in those patients who are just CR and MRD positive.”

“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena,” Dr Richardson contended. “The question for me, as a clinician, in my clinic, is ‘Do I apply it to everyday practice?’ And I would simply suggest to you, at this point, we’re not ready for that.”

Yes—MRD is ready for prime time

Dr Landgren based his argument on 2 meta-analyses published in 2016 and 2017 that outline the importance of MRD status in newly diagnosed MM patients.

The first analysis (Landgren et al 2016) showed that MRD negativity was associated with better PFS (hazard ratio [HR]=0.35] and OS (HR=0.48) than MRD positivity.

“So using more simple language,” Dr Landgren said, “this means that MRD negativity reduces the risk of progression by 65%, and it also reduces the risk of dying by 52%.”

The second analysis (Munshi et al 2017) also associated MRD-negative status with superior survival outcomes for both PFS (HR=0.41) and OS (HR=0.57).

As further confirmation of the importance of MRD status, the International Myeloma Working Group last year published response definitions that include MRD negativity at a sensitivity of 1 in 10⁵ cells or higher as the deepest level of treatment response in MM.

Dr Landgren drew on additional studies to support routine MRD testing in patient care.

The IFM Study Group found that, in newly diagnosed patients treated with lenalidomide, bortezomib, and dexamethasone followed by 1 year of lenalidomide maintenance, patients who received a subsequent transplant achieved superior outcomes compared to non-transplanted patients, in terms of CR (58% vs 46%) and 3-year PFS (61% vs 48%).

However, in patients who were MRD negative in both arms, the PFS rates were very similar, Dr Landgren said. And in terms of 3-year OS, there was no difference, at 88% in both arms.

The experience with daratumumab in relapsed/refractory patients exhibited a similar pattern.

The phase 3 POLLUX trial first showed that adding daratumumab to lenalidomide and dexamethasone was superior to lenalidomide and dexamethasone only, with a PFS at 18 months of 78% and 52%, respectively. This amounted to a 63% reduction in the risk of disease progression.

Investigators then took one more step forward, Dr Landgren said, and looked at MRD.

At a sensitivity of 10^-5, almost 25% of patients on the 3-drug regimen were MRD negative, “which is kind of amazing,” Dr Landgren said. “This is a very big step forward.”

“If you break down the results by MRD status, which is not the primary endpoint of the study, you see very similar patterns for PFS for MRD negative patients in each of the 2 arms,” he continued.

This raises the question of whether attaining MRD negativity is more important than the treatment modality.

MRD negativity has implications for speeding drug approvals, developing more sensitive assays, and future treatment management, Dr Landgren said.

No—MRD is not ready for prime time

Dr Richardson acknowledged that MRD assessment is important. However, he pointed out a number of caveats regarding how MRD assessment would be applied in clinical practice to support his position.

“I’d simply suggest to you that, in day-to-day practice, the definition [of MRD] is somewhat fluid,” he said. “And it varies, obviously, between diseases and technology used.”

For most malignancies, Dr Richardson said, 10⁹ to 10¹⁰ malignant cells are undetectable with conventional methods. These may or may not lead to a full clinical relapse within months or even years.

Using a sensitive technique to determine the presence of MRD could permit analysis of treatments that induce a greater depth of response or identify patients at risk of early relapse who need further treatment.

Dr Richardson enumerated hematologic malignancies that utilize MRD as secondary endpoints—acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

In chronic myeloid leukemia, MRD is used as a primary endpoint that dictates practice.

“And I would applaud the field in that area because, obviously, molecular response accepted as an endpoint by FDA for second-generation TKIs has been a bedrock of that approval process, and it now applies in clinical practice,” Dr Richardson said.

“Obviously, that’s where we’d like to be, but I’d suggest to you, just again, with a certain amount of moderation and a certain amount of caution, that we may not be quite there yet.”

Dr Richardson suggested that MRD assessment in MM is less advanced than in leukemia and lymphoma.

“[W]e are currently at the point where MRD assessments are clearly secondary endpoints, an important research tool,” he said.

Some “remarkable combination therapies,” he added, have abrogated some of the “extraordinary genetic complexity” in MM.

“The critical point here, though, is that, while we’re more successful in terms of these triplets and quadruplets and now with the introduction of monoclonal antibodies and similar approaches, we’re able to throw a bigger net around the disease,” Dr Richardson said.

“We’re not able to eradicate it completely, and cure remains, in myeloma, frankly, evasive. And I think that’s a critical point.”

Dr Richardson reviewed various strategies for molecular response monitoring, from flow cytometry to polymerase chain reaction and next-generation sequencing, noting that there is variance in applicability and sensitivity.

For example, the limits of detection among 91 labs ranged from 0.10% to 0.001%.

Dr Richardson returned to the “very robust” meta-analysis by Munshi and colleagues discussed by Dr Landgren.

While the authors’ analysis demonstrated that MRD is predictive of both longer PFS and OS, they concluded that the evidence supported MRD as an endpoint and research tool in clinical trials.

“So I would humbly suggest perhaps it’s not ready for clinical prime time yet,” Dr Richardson said.

He also referred to the IFM Study Group trial described by Dr Landgren, calling it a “critical forward effort.”

“[W]hat’s so interesting is that there was no difference in overall survival,” Dr Richardson said. “Now, that’s a very important point as we soberly look at these data and judge what they mean for each patient.”

And so Dr Richardson stood by his assessment that MRD is not yet a standard of care but may be one day. 

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from Wikipedia

The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.

Now, vemurafenib is the first FDA-approved treatment for ECD.

The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.

“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.

The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.

Image from Wikipedia

The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.

Now, vemurafenib is the first FDA-approved treatment for ECD.

The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.

“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.

The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.

Image from Wikipedia

The US Food and Drug Administration (FDA) has expanded the approved use of vemurafenib (Zelboraf) to include the treatment of adults who have Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug was already approved by the FDA to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test.

Now, vemurafenib is the first FDA-approved treatment for ECD.

The FDA previously granted vemurafenib orphan drug and breakthrough therapy designations for this indication, and the supplemental new drug application for vemurafenib in ECD received priority review.

“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”

The application for vemurafenib in ECD was supported by data from the phase 2 VE-BASKET study. Initial results from this study were published in NEJM in August 2015.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

In the 22 patients with ECD, the best overall response rate was 54.5%. Eleven patients experienced a partial response, and 1 patient achieved a complete response.

The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events (>50%) were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags. The most common grade 3 or higher adverse events (≥10%) were new skin cancers, high blood pressure, rash, and joint pain.

Photo courtesy of Janssen

NEW YORK, NY—The 4-year follow-up of the RESONATE trial suggests ibrutinib may provide long-term efficacy in previously treated patients with chronic lymphocytic leukemia (CLL).

The median progression-free survival (PFS) has not yet been reached in this trial, regardless of high-risk cytogenetics, according to Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

She presented the update at Lymphoma & Myeloma 2017. The follow-up study was awarded the best clinical CLL abstract of the meeting.

In the phase 3 RESONATE study, investigators compared ibrutinib—the first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase—to ofatumumab in previously treated CLL/small lymphocytic lymphoma (SLL).

The primary analysis showed ibrutinib significantly improved survival, with a 78% reduction in the risk of progression and a 57% reduction in the risk of death.

The phase 3 trial randomized 195 CLL/SLL patients to oral ibrutinib at 420 mg once daily and 196 patients to intravenous ofatumumab at an initial dose of 300 mg followed by 2000 mg for 11 doses over 24 weeks.

One hundred thirty-three patients progressed on ofatumumab and crossed over to receive once-daily ibrutinib.

Patient characteristics

In each arm, the median patient age was 67, more than half of patients had an ECOG status of 1, and more than half had advanced-stage disease.

High-risk genetic abnormalities were common, Dr Brown said, with deletion 11q in a third of patients in the ibrutinib arm and 31% in the ofatumumab arm. Another third in each arm had deletion 17p, while 51% in the ibrutinib arm and 46% in the ofatumumab arm had TP53 mutation.

About a quarter of the patients in each arm had complex karyotype, and 73% and 63% in the ibrutinib and ofatumumab arms, respectively, were IGHV-unmutated.

Survival

Ibrutinib significantly extended PFS compared with ofatumumab. At a median follow-up for ibrutinib of 44 months (range, 0.33 – 53), ibrutinib led to an 87% reduction in the risk of progression or death. The 3-year PFS rate was 59% with ibrutinib and 3% with ofatumumab.

Ibrutinib conferred a benefit in PFS across all baseline patient characteristics.

Among ibrutinib-treated patients, the 3-year PFS was 53% for patients with deletion 17p, 66% for those with deletion 11q but not deletion 17p, and 58% for those with neither abnormality.

Dr Brown noted how closely complex karyotype associates with high-risk cytogenetics. Forty-two percent of patients with 17p deletion had a complex karyotype, as did 23% of patients with 11q deletion and 15% of patients with neither 17p nor 11q deletion.

For IGHV-mutation status, Dr Brown said there is no difference in PFS with this degree of follow-up.

In terms of TP53 mutation status, Dr Brown pointed out a trend toward a worse PFS in those patients with the mutation.

“We actually looked by individual p53 mutation versus 17p deletion, versus both, versus neither, in the 2-year follow-up paper and found that p53 with 17p, both abnormalities, did have worse PFS than neither,” she said.

“This may require further follow-up because we do know that most 17p patients also have a p53 mutation, particularly in the relapsed setting.”

As expected, Dr Brown said, those patients with more than 2 prior therapies had a worse PFS compared to patients with 2 or fewer prior therapies.

Multivariate analysis demonstrated that more than 2 prior lines of therapy or an elevated ß2 microglobulin were associated with decreased PFS with ibrutinib.

When the investigators adjusted the overall survival data for cross-over, ibrutinib was projected to continue the overall survival benefit compared with ofatumumab, with a hazard ratio of 0.37.

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.

Photo courtesy of Janssen

NEW YORK, NY—The 4-year follow-up of the RESONATE trial suggests ibrutinib may provide long-term efficacy in previously treated patients with chronic lymphocytic leukemia (CLL).

The median progression-free survival (PFS) has not yet been reached in this trial, regardless of high-risk cytogenetics, according to Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

She presented the update at Lymphoma & Myeloma 2017. The follow-up study was awarded the best clinical CLL abstract of the meeting.

In the phase 3 RESONATE study, investigators compared ibrutinib—the first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase—to ofatumumab in previously treated CLL/small lymphocytic lymphoma (SLL).

The primary analysis showed ibrutinib significantly improved survival, with a 78% reduction in the risk of progression and a 57% reduction in the risk of death.

The phase 3 trial randomized 195 CLL/SLL patients to oral ibrutinib at 420 mg once daily and 196 patients to intravenous ofatumumab at an initial dose of 300 mg followed by 2000 mg for 11 doses over 24 weeks.

One hundred thirty-three patients progressed on ofatumumab and crossed over to receive once-daily ibrutinib.

Patient characteristics

In each arm, the median patient age was 67, more than half of patients had an ECOG status of 1, and more than half had advanced-stage disease.

High-risk genetic abnormalities were common, Dr Brown said, with deletion 11q in a third of patients in the ibrutinib arm and 31% in the ofatumumab arm. Another third in each arm had deletion 17p, while 51% in the ibrutinib arm and 46% in the ofatumumab arm had TP53 mutation.

About a quarter of the patients in each arm had complex karyotype, and 73% and 63% in the ibrutinib and ofatumumab arms, respectively, were IGHV-unmutated.

Survival

Ibrutinib significantly extended PFS compared with ofatumumab. At a median follow-up for ibrutinib of 44 months (range, 0.33 – 53), ibrutinib led to an 87% reduction in the risk of progression or death. The 3-year PFS rate was 59% with ibrutinib and 3% with ofatumumab.

Ibrutinib conferred a benefit in PFS across all baseline patient characteristics.

Among ibrutinib-treated patients, the 3-year PFS was 53% for patients with deletion 17p, 66% for those with deletion 11q but not deletion 17p, and 58% for those with neither abnormality.

Dr Brown noted how closely complex karyotype associates with high-risk cytogenetics. Forty-two percent of patients with 17p deletion had a complex karyotype, as did 23% of patients with 11q deletion and 15% of patients with neither 17p nor 11q deletion.

For IGHV-mutation status, Dr Brown said there is no difference in PFS with this degree of follow-up.

In terms of TP53 mutation status, Dr Brown pointed out a trend toward a worse PFS in those patients with the mutation.

“We actually looked by individual p53 mutation versus 17p deletion, versus both, versus neither, in the 2-year follow-up paper and found that p53 with 17p, both abnormalities, did have worse PFS than neither,” she said.

“This may require further follow-up because we do know that most 17p patients also have a p53 mutation, particularly in the relapsed setting.”

As expected, Dr Brown said, those patients with more than 2 prior therapies had a worse PFS compared to patients with 2 or fewer prior therapies.

Multivariate analysis demonstrated that more than 2 prior lines of therapy or an elevated ß2 microglobulin were associated with decreased PFS with ibrutinib.

When the investigators adjusted the overall survival data for cross-over, ibrutinib was projected to continue the overall survival benefit compared with ofatumumab, with a hazard ratio of 0.37.

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.

Photo courtesy of Janssen

NEW YORK, NY—The 4-year follow-up of the RESONATE trial suggests ibrutinib may provide long-term efficacy in previously treated patients with chronic lymphocytic leukemia (CLL).

The median progression-free survival (PFS) has not yet been reached in this trial, regardless of high-risk cytogenetics, according to Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

She presented the update at Lymphoma & Myeloma 2017. The follow-up study was awarded the best clinical CLL abstract of the meeting.

In the phase 3 RESONATE study, investigators compared ibrutinib—the first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase—to ofatumumab in previously treated CLL/small lymphocytic lymphoma (SLL).

The primary analysis showed ibrutinib significantly improved survival, with a 78% reduction in the risk of progression and a 57% reduction in the risk of death.

The phase 3 trial randomized 195 CLL/SLL patients to oral ibrutinib at 420 mg once daily and 196 patients to intravenous ofatumumab at an initial dose of 300 mg followed by 2000 mg for 11 doses over 24 weeks.

One hundred thirty-three patients progressed on ofatumumab and crossed over to receive once-daily ibrutinib.

Patient characteristics

In each arm, the median patient age was 67, more than half of patients had an ECOG status of 1, and more than half had advanced-stage disease.

High-risk genetic abnormalities were common, Dr Brown said, with deletion 11q in a third of patients in the ibrutinib arm and 31% in the ofatumumab arm. Another third in each arm had deletion 17p, while 51% in the ibrutinib arm and 46% in the ofatumumab arm had TP53 mutation.

About a quarter of the patients in each arm had complex karyotype, and 73% and 63% in the ibrutinib and ofatumumab arms, respectively, were IGHV-unmutated.

Survival

Ibrutinib significantly extended PFS compared with ofatumumab. At a median follow-up for ibrutinib of 44 months (range, 0.33 – 53), ibrutinib led to an 87% reduction in the risk of progression or death. The 3-year PFS rate was 59% with ibrutinib and 3% with ofatumumab.

Ibrutinib conferred a benefit in PFS across all baseline patient characteristics.

Among ibrutinib-treated patients, the 3-year PFS was 53% for patients with deletion 17p, 66% for those with deletion 11q but not deletion 17p, and 58% for those with neither abnormality.

Dr Brown noted how closely complex karyotype associates with high-risk cytogenetics. Forty-two percent of patients with 17p deletion had a complex karyotype, as did 23% of patients with 11q deletion and 15% of patients with neither 17p nor 11q deletion.

For IGHV-mutation status, Dr Brown said there is no difference in PFS with this degree of follow-up.

In terms of TP53 mutation status, Dr Brown pointed out a trend toward a worse PFS in those patients with the mutation.

“We actually looked by individual p53 mutation versus 17p deletion, versus both, versus neither, in the 2-year follow-up paper and found that p53 with 17p, both abnormalities, did have worse PFS than neither,” she said.

“This may require further follow-up because we do know that most 17p patients also have a p53 mutation, particularly in the relapsed setting.”

As expected, Dr Brown said, those patients with more than 2 prior therapies had a worse PFS compared to patients with 2 or fewer prior therapies.

Multivariate analysis demonstrated that more than 2 prior lines of therapy or an elevated ß2 microglobulin were associated with decreased PFS with ibrutinib.

When the investigators adjusted the overall survival data for cross-over, ibrutinib was projected to continue the overall survival benefit compared with ofatumumab, with a hazard ratio of 0.37.

Response rates

Dr Brown noted that, early on, there’s quite a significant rate of partial response with lymphocytosis observed in patients on ibrutinib.

This “diminishes dramatically,” she said, but about 5% of patients at 3 and 4 years still have ongoing lymphocytosis.

“Similarly, initially, there’s a very low rate of complete remission, which has risen steadily to 9% at this follow-up,” she said.

And the overall response rate is 91%.

Treatment exposure and toxicity

The median duration of ibrutinib treatment is 41 months, and 46% of patients continue on treatment. Twenty-seven percent of patients discontinued due to progression, and 12% because of adverse events (AEs).

Of the 53 patients who discontinued therapy, 14 had transformation as their primary reason, 9 with diffuse large B-cell lymphoma, 3 with Hodgkin disease, and 2 with prolymphocytic lymphoma.

The most frequent AEs leading to discontinuation included pneumonia (n=3), anemia (n=2), thrombocytopenia (n=2), diarrhea (n=2), and anal incontinence (n=2).

AEs leading to discontinuation decreased over time—6% in year 0 to 1 and 4% in years 2 to 3.

“The most frequent cumulative AEs are similar to what we’ve seen in most prior studies,” Dr Brown said, including diarrhea, fatigue, and cough.

In terms of grade 3 or higher AEs, about a quarter of patients had neutropenia, 17% had pneumonia, and 8% had hypertension.

Six percent of patients had major hemorrhage, and all-grade atrial fibrillation occurred in 11% of patients.

“Now, many of the grade 3 and higher AEs did decline over time during the study,” Dr Brown noted. “You can see this is quite evident for neutropenia as well as pneumonia, and all infections declined from year 1 to subsequent years.”

Hypertension, in contrast, has been fairly steady over the later years, she said, and atrial fibrillation is highest in the first 6 months but then continues at a low rate thereafter.

The investigators believe these long-term results demonstrate that ibrutinib is tolerable and continues to show sustained efficacy in previously treated and high-genomic-risk patients with CLL. In addition, no long-term safety signals have emerged.

This study was sponsored by Pharmacyclics, LLC, an AbbVie company.

Red and white blood cells

The US Food and Drug Administration (FDA) has expanded the approved use of the XW-100 Automated Hematology Analyzer.

The analyzer can now be used at non-traditional laboratory sites by non-medical personnel.

The XW-100 Automated Hematology Analyzer is intended for use in patients age 2 and older who require a whole blood cell count and white blood cell differential.

Test results can be used with other clinical and laboratory findings to provide early alerts of patients with serious conditions, such as severe anemia and agranulocytosis, who require additional testing.

The XW-100 Automated Hematology Analyzer is not intended to diagnose or monitor patients with primary and/or secondary hematologic diseases.

The device works by using a blood sample to classify and quantify 12 hematology parameters, which provides patients with a blood component profile as part of their overall health assessment.

Expanded clearance

The FDA granted the XW-100 Automated Hematology Analyzer a waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The waiver allows the device to be used by a variety of non-traditional laboratory sites, including physicians’ offices, clinics, or other types of healthcare facilities with a CLIA Certificate of Waiver.

The XW-100 Automated Hematology Analyzer was reviewed through the dual submission pathway, a streamlined regulatory pathway for 510(k) marketing clearance and CLIA Waiver by Application.

A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The XW-100 Automated Hematology Analyzer was originally cleared through the 510(k) pathway in 2015 for use at the patient’s point-of-care.

To support the use of this device in CLIA-waived settings with non-medical personnel, the analyzer is now accompanied by simple instructions for operator actions when results are flagged or outside of a specified range.

To further ensure accurate testing in this setting and to eliminate results that are most susceptible to inaccuracy or require additional testing, the number of hematology parameters has been reduced to 12.

The FDA found this modified version of the XW-100 Automated Hematology Analyzer to be substantially equivalent to the 2015 model.

In addition, data submitted by Sysmex America, Inc. (the company marketing the analyzer) demonstrated ease of use and a low risk of false results when the modified XW-100 Automated Hematology Analyzer was used by untrained operators.

The FDA reviewed data from a study conducted on 582 samples collected from patients ages 2 to 92.

In this study, researchers compared XW-100 Automated Hematology Analyzer results collected by non-medical personnel in CLIA-waived settings to results from a hematology analyzer in an accredited clinical laboratory.

Results showed that, by following the manufacturer’s instructions for use, accurate testing can be effectively conducted by untrained personnel.

Red and white blood cells

The US Food and Drug Administration (FDA) has expanded the approved use of the XW-100 Automated Hematology Analyzer.

The analyzer can now be used at non-traditional laboratory sites by non-medical personnel.

The XW-100 Automated Hematology Analyzer is intended for use in patients age 2 and older who require a whole blood cell count and white blood cell differential.

Test results can be used with other clinical and laboratory findings to provide early alerts of patients with serious conditions, such as severe anemia and agranulocytosis, who require additional testing.

The XW-100 Automated Hematology Analyzer is not intended to diagnose or monitor patients with primary and/or secondary hematologic diseases.

The device works by using a blood sample to classify and quantify 12 hematology parameters, which provides patients with a blood component profile as part of their overall health assessment.

Expanded clearance

The FDA granted the XW-100 Automated Hematology Analyzer a waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The waiver allows the device to be used by a variety of non-traditional laboratory sites, including physicians’ offices, clinics, or other types of healthcare facilities with a CLIA Certificate of Waiver.

The XW-100 Automated Hematology Analyzer was reviewed through the dual submission pathway, a streamlined regulatory pathway for 510(k) marketing clearance and CLIA Waiver by Application.

A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The XW-100 Automated Hematology Analyzer was originally cleared through the 510(k) pathway in 2015 for use at the patient’s point-of-care.

To support the use of this device in CLIA-waived settings with non-medical personnel, the analyzer is now accompanied by simple instructions for operator actions when results are flagged or outside of a specified range.

To further ensure accurate testing in this setting and to eliminate results that are most susceptible to inaccuracy or require additional testing, the number of hematology parameters has been reduced to 12.

The FDA found this modified version of the XW-100 Automated Hematology Analyzer to be substantially equivalent to the 2015 model.

In addition, data submitted by Sysmex America, Inc. (the company marketing the analyzer) demonstrated ease of use and a low risk of false results when the modified XW-100 Automated Hematology Analyzer was used by untrained operators.

The FDA reviewed data from a study conducted on 582 samples collected from patients ages 2 to 92.

In this study, researchers compared XW-100 Automated Hematology Analyzer results collected by non-medical personnel in CLIA-waived settings to results from a hematology analyzer in an accredited clinical laboratory.

Results showed that, by following the manufacturer’s instructions for use, accurate testing can be effectively conducted by untrained personnel.

Red and white blood cells

The US Food and Drug Administration (FDA) has expanded the approved use of the XW-100 Automated Hematology Analyzer.

The analyzer can now be used at non-traditional laboratory sites by non-medical personnel.

The XW-100 Automated Hematology Analyzer is intended for use in patients age 2 and older who require a whole blood cell count and white blood cell differential.

Test results can be used with other clinical and laboratory findings to provide early alerts of patients with serious conditions, such as severe anemia and agranulocytosis, who require additional testing.

The XW-100 Automated Hematology Analyzer is not intended to diagnose or monitor patients with primary and/or secondary hematologic diseases.

The device works by using a blood sample to classify and quantify 12 hematology parameters, which provides patients with a blood component profile as part of their overall health assessment.

Expanded clearance

The FDA granted the XW-100 Automated Hematology Analyzer a waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The waiver allows the device to be used by a variety of non-traditional laboratory sites, including physicians’ offices, clinics, or other types of healthcare facilities with a CLIA Certificate of Waiver.

The XW-100 Automated Hematology Analyzer was reviewed through the dual submission pathway, a streamlined regulatory pathway for 510(k) marketing clearance and CLIA Waiver by Application.

A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The XW-100 Automated Hematology Analyzer was originally cleared through the 510(k) pathway in 2015 for use at the patient’s point-of-care.

To support the use of this device in CLIA-waived settings with non-medical personnel, the analyzer is now accompanied by simple instructions for operator actions when results are flagged or outside of a specified range.

To further ensure accurate testing in this setting and to eliminate results that are most susceptible to inaccuracy or require additional testing, the number of hematology parameters has been reduced to 12.

The FDA found this modified version of the XW-100 Automated Hematology Analyzer to be substantially equivalent to the 2015 model.

In addition, data submitted by Sysmex America, Inc. (the company marketing the analyzer) demonstrated ease of use and a low risk of false results when the modified XW-100 Automated Hematology Analyzer was used by untrained operators.

The FDA reviewed data from a study conducted on 582 samples collected from patients ages 2 to 92.

In this study, researchers compared XW-100 Automated Hematology Analyzer results collected by non-medical personnel in CLIA-waived settings to results from a hematology analyzer in an accredited clinical laboratory.

Results showed that, by following the manufacturer’s instructions for use, accurate testing can be effectively conducted by untrained personnel.

Photo by Rhoda Baer

SAN DIEGO—New research suggests an intervention can improve psychosocial health in adolescents and young adults (AYAs) living with cancer.

The intervention, Promoting Resilience in Stress Management (PRISM), is designed to help patients manage stress, set goals, and change their perspective.

Overall, PRISM improved resilience, enhanced quality of life, increased hope, and lowered distress and depression in the patients studied.

Abby R. Rosenberg, MD, of Seattle Children’s Research Institute in Seattle, Washington, presented these results at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 176*).

“The experience of cancer is stressful in all realms, but we tend to focus more on physical symptoms than the equally important social and emotional challenges,” Dr Rosenberg said.

“This is particularly true for adolescents and young adults who already struggle with normal developmental changes. When you throw cancer into the mix, it can become much harder.”

With this in mind, Dr Rosenberg and her colleagues tested PRISM in AYAs with cancer. The trial included 99 English-speaking patients, ages 12 to 25, who were diagnosed with new or newly recurrent cancer.

The patients were randomized to receive PRISM (n=49) plus standard psychosocial supportive care or standard care alone (n=50). Standard care at Seattle Children’s Research Institute includes a dedicated social worker and access to psychologists, child-life specialists, and other experts in AYA oncology care, as needed.

PRISM targets 4 topics:

• Managing stress with skills based on mindfulness and relaxation
• Setting goals that are specific and realistic, as well as planning for roadblocks
• Positive reframing, or recognizing and replacing negative self-talk
• Making meaning, or identifying benefits, gratitude, purpose, and legacy.

Each of the 4 topics were discussed with patients in separate, one-on-one sessions with a trained research associate. The sessions lasted 30 minutes to an hour. Patients also received boosters and worksheets for practicing the skills discussed in the meetings.

After all 4 sessions had been completed, patients could participate in an optional family meeting. During this meeting, patients could discuss with their family members which aspects of PRISM worked.

Results

Patients completed surveys at study enrollment, 2 months, 4 months, and 6 months. There were 74 participants who were still alive and well enough to complete the 6-month survey—36 in the PRISM group and 38 in the control group.

At the 6-month mark, PRISM was associated with (sometimes significant) improvements in resilience (P=0.02), generic quality of life (P=0.08), cancer-specific quality of life (P=0.01), hope (P=0.34), and distress (P=0.03). (P values are for absolute difference from baseline to 6 months.)

In addition, the incidence of depression at 6 months was lower in the PRISM group than the control group—6% and 21%, respectively (odds ratio=0.09, 95% CI 0.01, 1.09).

All but 4 of the PRISM recipients chose to participate in the family meeting following their one-on-one sessions.

“We included the family meeting because teens told us they wanted to share with their parents, and parents told us they wanted to know what their children had learned,” Dr Rosenberg said. “While the specific impact of this meeting is yet to be determined, we hope it will guide families so that there is continued support of teen or young adult patients.”

Now, Dr Rosenberg and her colleagues would like to test PRISM in other patient populations.

“We need to include a much larger cultural demographic in future studies,” Dr Rosenberg noted. “Beyond that, we also need to determine if this type of intervention could translate to other centers where usual care may not be as comprehensive as what we have here.”

*Some data in the abstract differ from the presentation.

Photo by Rhoda Baer

SAN DIEGO—New research suggests an intervention can improve psychosocial health in adolescents and young adults (AYAs) living with cancer.

The intervention, Promoting Resilience in Stress Management (PRISM), is designed to help patients manage stress, set goals, and change their perspective.

Overall, PRISM improved resilience, enhanced quality of life, increased hope, and lowered distress and depression in the patients studied.

Abby R. Rosenberg, MD, of Seattle Children’s Research Institute in Seattle, Washington, presented these results at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 176*).

“The experience of cancer is stressful in all realms, but we tend to focus more on physical symptoms than the equally important social and emotional challenges,” Dr Rosenberg said.

“This is particularly true for adolescents and young adults who already struggle with normal developmental changes. When you throw cancer into the mix, it can become much harder.”

With this in mind, Dr Rosenberg and her colleagues tested PRISM in AYAs with cancer. The trial included 99 English-speaking patients, ages 12 to 25, who were diagnosed with new or newly recurrent cancer.

The patients were randomized to receive PRISM (n=49) plus standard psychosocial supportive care or standard care alone (n=50). Standard care at Seattle Children’s Research Institute includes a dedicated social worker and access to psychologists, child-life specialists, and other experts in AYA oncology care, as needed.

PRISM targets 4 topics:

• Managing stress with skills based on mindfulness and relaxation
• Setting goals that are specific and realistic, as well as planning for roadblocks
• Positive reframing, or recognizing and replacing negative self-talk
• Making meaning, or identifying benefits, gratitude, purpose, and legacy.

Each of the 4 topics were discussed with patients in separate, one-on-one sessions with a trained research associate. The sessions lasted 30 minutes to an hour. Patients also received boosters and worksheets for practicing the skills discussed in the meetings.

After all 4 sessions had been completed, patients could participate in an optional family meeting. During this meeting, patients could discuss with their family members which aspects of PRISM worked.

Results

Patients completed surveys at study enrollment, 2 months, 4 months, and 6 months. There were 74 participants who were still alive and well enough to complete the 6-month survey—36 in the PRISM group and 38 in the control group.

At the 6-month mark, PRISM was associated with (sometimes significant) improvements in resilience (P=0.02), generic quality of life (P=0.08), cancer-specific quality of life (P=0.01), hope (P=0.34), and distress (P=0.03). (P values are for absolute difference from baseline to 6 months.)

In addition, the incidence of depression at 6 months was lower in the PRISM group than the control group—6% and 21%, respectively (odds ratio=0.09, 95% CI 0.01, 1.09).

All but 4 of the PRISM recipients chose to participate in the family meeting following their one-on-one sessions.

“We included the family meeting because teens told us they wanted to share with their parents, and parents told us they wanted to know what their children had learned,” Dr Rosenberg said. “While the specific impact of this meeting is yet to be determined, we hope it will guide families so that there is continued support of teen or young adult patients.”

Now, Dr Rosenberg and her colleagues would like to test PRISM in other patient populations.

“We need to include a much larger cultural demographic in future studies,” Dr Rosenberg noted. “Beyond that, we also need to determine if this type of intervention could translate to other centers where usual care may not be as comprehensive as what we have here.”

*Some data in the abstract differ from the presentation.

Photo by Rhoda Baer

SAN DIEGO—New research suggests an intervention can improve psychosocial health in adolescents and young adults (AYAs) living with cancer.

The intervention, Promoting Resilience in Stress Management (PRISM), is designed to help patients manage stress, set goals, and change their perspective.

Overall, PRISM improved resilience, enhanced quality of life, increased hope, and lowered distress and depression in the patients studied.

Abby R. Rosenberg, MD, of Seattle Children’s Research Institute in Seattle, Washington, presented these results at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 176*).

“The experience of cancer is stressful in all realms, but we tend to focus more on physical symptoms than the equally important social and emotional challenges,” Dr Rosenberg said.

“This is particularly true for adolescents and young adults who already struggle with normal developmental changes. When you throw cancer into the mix, it can become much harder.”

With this in mind, Dr Rosenberg and her colleagues tested PRISM in AYAs with cancer. The trial included 99 English-speaking patients, ages 12 to 25, who were diagnosed with new or newly recurrent cancer.

The patients were randomized to receive PRISM (n=49) plus standard psychosocial supportive care or standard care alone (n=50). Standard care at Seattle Children’s Research Institute includes a dedicated social worker and access to psychologists, child-life specialists, and other experts in AYA oncology care, as needed.

PRISM targets 4 topics:

• Managing stress with skills based on mindfulness and relaxation
• Setting goals that are specific and realistic, as well as planning for roadblocks
• Positive reframing, or recognizing and replacing negative self-talk
• Making meaning, or identifying benefits, gratitude, purpose, and legacy.

Each of the 4 topics were discussed with patients in separate, one-on-one sessions with a trained research associate. The sessions lasted 30 minutes to an hour. Patients also received boosters and worksheets for practicing the skills discussed in the meetings.

After all 4 sessions had been completed, patients could participate in an optional family meeting. During this meeting, patients could discuss with their family members which aspects of PRISM worked.

Results

Patients completed surveys at study enrollment, 2 months, 4 months, and 6 months. There were 74 participants who were still alive and well enough to complete the 6-month survey—36 in the PRISM group and 38 in the control group.

At the 6-month mark, PRISM was associated with (sometimes significant) improvements in resilience (P=0.02), generic quality of life (P=0.08), cancer-specific quality of life (P=0.01), hope (P=0.34), and distress (P=0.03). (P values are for absolute difference from baseline to 6 months.)

In addition, the incidence of depression at 6 months was lower in the PRISM group than the control group—6% and 21%, respectively (odds ratio=0.09, 95% CI 0.01, 1.09).

All but 4 of the PRISM recipients chose to participate in the family meeting following their one-on-one sessions.

“We included the family meeting because teens told us they wanted to share with their parents, and parents told us they wanted to know what their children had learned,” Dr Rosenberg said. “While the specific impact of this meeting is yet to be determined, we hope it will guide families so that there is continued support of teen or young adult patients.”

Now, Dr Rosenberg and her colleagues would like to test PRISM in other patient populations.

“We need to include a much larger cultural demographic in future studies,” Dr Rosenberg noted. “Beyond that, we also need to determine if this type of intervention could translate to other centers where usual care may not be as comprehensive as what we have here.”

*Some data in the abstract differ from the presentation.