Lymphoma & Plasma Cell Disorders

Lenalidomide alone and in combination showed “clinically significant activity” and no new safety signals in patients with mantle cell lymphoma (MCL) who had previously failed on ibrutinib, according to findings from a retrospective, observational study.

Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues enrolled 58 MCL patients across 11 study sites. The patients had a median age of 71 years and 88% of patients had received three or more prior therapies. Most had received ibrutinib as monotherapy and used a lenalidomide-containing therapy next.

The overall response rate was 29% (95% confidence interval, 18%-43%). The rate was similar between patients with MCL refractory to ibrutinib and patients who relapsed/progressed on or following ibrutinib use (32% versus 30%, respectively). There was a 14% complete response, though it varied by subgroup with 8% among MCL patients refractory to ibrutinib and 22% among relapsed/progressed patients. There was a 20-week median duration of response, but 82% of responders were censored so the researchers urged caution in interpreting that finding.

Among the 58 patients, more than 80% reported one or more treatment-emergent adverse events during lenalidomide treatment and 20 patients (34%) had serious events. Nine patients (16%) discontinued the drug because of adverse events.

“Lenalidomide addresses an unmet medical need and widens the therapeutic options in a difficult-to-treat patient population,” the researchers wrote.

Read the full study in the Journal of Hematology Oncology (2017 Nov 2;10[1]:171).

mschneider@frontlinemedcom.com

On Twitter @maryellenny

Lenalidomide alone and in combination showed “clinically significant activity” and no new safety signals in patients with mantle cell lymphoma (MCL) who had previously failed on ibrutinib, according to findings from a retrospective, observational study.

Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues enrolled 58 MCL patients across 11 study sites. The patients had a median age of 71 years and 88% of patients had received three or more prior therapies. Most had received ibrutinib as monotherapy and used a lenalidomide-containing therapy next.

The overall response rate was 29% (95% confidence interval, 18%-43%). The rate was similar between patients with MCL refractory to ibrutinib and patients who relapsed/progressed on or following ibrutinib use (32% versus 30%, respectively). There was a 14% complete response, though it varied by subgroup with 8% among MCL patients refractory to ibrutinib and 22% among relapsed/progressed patients. There was a 20-week median duration of response, but 82% of responders were censored so the researchers urged caution in interpreting that finding.

Among the 58 patients, more than 80% reported one or more treatment-emergent adverse events during lenalidomide treatment and 20 patients (34%) had serious events. Nine patients (16%) discontinued the drug because of adverse events.

“Lenalidomide addresses an unmet medical need and widens the therapeutic options in a difficult-to-treat patient population,” the researchers wrote.

Read the full study in the Journal of Hematology Oncology (2017 Nov 2;10[1]:171).

mschneider@frontlinemedcom.com

On Twitter @maryellenny

Lenalidomide alone and in combination showed “clinically significant activity” and no new safety signals in patients with mantle cell lymphoma (MCL) who had previously failed on ibrutinib, according to findings from a retrospective, observational study.

Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues enrolled 58 MCL patients across 11 study sites. The patients had a median age of 71 years and 88% of patients had received three or more prior therapies. Most had received ibrutinib as monotherapy and used a lenalidomide-containing therapy next.

The overall response rate was 29% (95% confidence interval, 18%-43%). The rate was similar between patients with MCL refractory to ibrutinib and patients who relapsed/progressed on or following ibrutinib use (32% versus 30%, respectively). There was a 14% complete response, though it varied by subgroup with 8% among MCL patients refractory to ibrutinib and 22% among relapsed/progressed patients. There was a 20-week median duration of response, but 82% of responders were censored so the researchers urged caution in interpreting that finding.

Among the 58 patients, more than 80% reported one or more treatment-emergent adverse events during lenalidomide treatment and 20 patients (34%) had serious events. Nine patients (16%) discontinued the drug because of adverse events.

“Lenalidomide addresses an unmet medical need and widens the therapeutic options in a difficult-to-treat patient population,” the researchers wrote.

Read the full study in the Journal of Hematology Oncology (2017 Nov 2;10[1]:171).

mschneider@frontlinemedcom.com

On Twitter @maryellenny

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

lnikolaides@frontlinemedcom.com

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

lnikolaides@frontlinemedcom.com

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

lnikolaides@frontlinemedcom.com

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.

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.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo by Bill Branson

Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*

Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.

Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).

The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).

For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.

To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.

Results

The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).

The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).

Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.

Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).

Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.

Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.

The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.

The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.

This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).

*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.

Photo courtesy of NIH

SAN DIEGO—A new study suggests patients with advanced cancer may prefer doctors who do not use a computer while communicating with them.

Most of the 120 patients studied said they preferred face-to-face consultations in which a doctor used a notepad rather than a computer.

Doctors who did not use a computer were perceived as more compassionate, communicative, and professional.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 26*).

“To our knowledge, this is the only study that compares exam room interactions between people with advanced cancer and their physicians, with or without a computer present,” said study investigator Ali Haider, MD, of the University of Texas MD Anderson Cancer Center in Houston.

For this study, Dr Haider and his colleagues enrolled 120 patients with localized, recurrent, or metastatic disease. The patients’ median ECOG performance status was 2.

All patients were English speakers, they had a median age of 58 (range, 44-66), and 55% were female. Sixty-seven percent of patients were white, 18% were Hispanic, 13% were African American, and 2% were “other.” Forty-one percent of patients had completed college.

According to the Edmonton Symptom Assessment System, patients’ median pain score was 5 (range, 2-7), and their median fatigue score was 4 (range, 3-7). According to the Hospital Anxiety and Depression Scale, patients’ median anxiety score was 6 (range, 4-8), and their median depression score was 6 (range, 4-9).

The intervention

The investigators randomly assigned patients to watch different videos showing doctor-patient interactions with and without computer use. The team had filmed 4 short videos that featured actors playing the parts of doctor and patient.

All study participants were blinded to the hypothesis of the study. The actors were carefully scripted and used the same gestures, expressions, and other nonverbal communication in each video to minimize bias.

Video 1 involved Doctor A in a face-to-face consultation with just a notepad in hand, and Video 2 involved Doctor A in a consultation using a computer.

Video 3 involved Doctor B in a face-to-face consultation with just a notepad in hand, and Video 4 involved Doctor B in a consultation using a computer.

Doctors A and B looked similar, which was intended to minimize bias.

After viewing their first video, patients completed a validated questionnaire rating the doctor’s communication skills, professionalism, and compassion.

Subsequently, each group was assigned to a video topic (face-to-face or computer) they had not viewed previously featuring the doctor they had not viewed in the first video.

A follow-up questionnaire was given after this round of viewing, and the patients were also asked to rate their overall physician preference.

Results

After the first round of viewing, the patients gave better ratings to doctors (A or B) in the face-to-face videos than in the computer videos. Face-to-face doctors were rated significantly higher for compassion (P=0.0003), communication skills (P=0.0012), and professionalism (P=0.0001).

After patients had watched both videos, doctors in the face-to-face videos still had better scores for compassion, communication, and professionalism (P<0.001 for all).

Most patients (72%) said they preferred the face-to-face consultation, while 8% said they preferred the computer consultation, and 20% said they had no preference.

Dr Haider said a possible explanation for these findings is that patients with serious chronic illnesses might value undivided attention from their physicians, and patients might perceive providers using computers as more distracted or multitasking during visits.

“We know that having a good rapport with patients can be extremely beneficial for their health,” Dr Haider said. “Patients with advanced disease need the cues that come with direct interaction to help them along with their care.”

However, Dr Haider also noted that additional research is needed to confirm these results. And he said perceptions might be different in a younger population with higher computer literacy.

*Data in the abstract differ from the presentation.

Photo courtesy of NIH

SAN DIEGO—A new study suggests patients with advanced cancer may prefer doctors who do not use a computer while communicating with them.

Most of the 120 patients studied said they preferred face-to-face consultations in which a doctor used a notepad rather than a computer.

Doctors who did not use a computer were perceived as more compassionate, communicative, and professional.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 26*).

“To our knowledge, this is the only study that compares exam room interactions between people with advanced cancer and their physicians, with or without a computer present,” said study investigator Ali Haider, MD, of the University of Texas MD Anderson Cancer Center in Houston.

For this study, Dr Haider and his colleagues enrolled 120 patients with localized, recurrent, or metastatic disease. The patients’ median ECOG performance status was 2.

All patients were English speakers, they had a median age of 58 (range, 44-66), and 55% were female. Sixty-seven percent of patients were white, 18% were Hispanic, 13% were African American, and 2% were “other.” Forty-one percent of patients had completed college.

According to the Edmonton Symptom Assessment System, patients’ median pain score was 5 (range, 2-7), and their median fatigue score was 4 (range, 3-7). According to the Hospital Anxiety and Depression Scale, patients’ median anxiety score was 6 (range, 4-8), and their median depression score was 6 (range, 4-9).

The intervention

The investigators randomly assigned patients to watch different videos showing doctor-patient interactions with and without computer use. The team had filmed 4 short videos that featured actors playing the parts of doctor and patient.

All study participants were blinded to the hypothesis of the study. The actors were carefully scripted and used the same gestures, expressions, and other nonverbal communication in each video to minimize bias.

Video 1 involved Doctor A in a face-to-face consultation with just a notepad in hand, and Video 2 involved Doctor A in a consultation using a computer.

Video 3 involved Doctor B in a face-to-face consultation with just a notepad in hand, and Video 4 involved Doctor B in a consultation using a computer.

Doctors A and B looked similar, which was intended to minimize bias.

After viewing their first video, patients completed a validated questionnaire rating the doctor’s communication skills, professionalism, and compassion.

Subsequently, each group was assigned to a video topic (face-to-face or computer) they had not viewed previously featuring the doctor they had not viewed in the first video.

A follow-up questionnaire was given after this round of viewing, and the patients were also asked to rate their overall physician preference.

Results

After the first round of viewing, the patients gave better ratings to doctors (A or B) in the face-to-face videos than in the computer videos. Face-to-face doctors were rated significantly higher for compassion (P=0.0003), communication skills (P=0.0012), and professionalism (P=0.0001).

After patients had watched both videos, doctors in the face-to-face videos still had better scores for compassion, communication, and professionalism (P<0.001 for all).

Most patients (72%) said they preferred the face-to-face consultation, while 8% said they preferred the computer consultation, and 20% said they had no preference.

Dr Haider said a possible explanation for these findings is that patients with serious chronic illnesses might value undivided attention from their physicians, and patients might perceive providers using computers as more distracted or multitasking during visits.

“We know that having a good rapport with patients can be extremely beneficial for their health,” Dr Haider said. “Patients with advanced disease need the cues that come with direct interaction to help them along with their care.”

However, Dr Haider also noted that additional research is needed to confirm these results. And he said perceptions might be different in a younger population with higher computer literacy.

*Data in the abstract differ from the presentation.

Photo courtesy of NIH

SAN DIEGO—A new study suggests patients with advanced cancer may prefer doctors who do not use a computer while communicating with them.

Most of the 120 patients studied said they preferred face-to-face consultations in which a doctor used a notepad rather than a computer.

Doctors who did not use a computer were perceived as more compassionate, communicative, and professional.

These findings were presented at the 2017 Palliative and Supportive Care in Oncology Symposium (abstract 26*).

“To our knowledge, this is the only study that compares exam room interactions between people with advanced cancer and their physicians, with or without a computer present,” said study investigator Ali Haider, MD, of the University of Texas MD Anderson Cancer Center in Houston.

For this study, Dr Haider and his colleagues enrolled 120 patients with localized, recurrent, or metastatic disease. The patients’ median ECOG performance status was 2.

All patients were English speakers, they had a median age of 58 (range, 44-66), and 55% were female. Sixty-seven percent of patients were white, 18% were Hispanic, 13% were African American, and 2% were “other.” Forty-one percent of patients had completed college.

According to the Edmonton Symptom Assessment System, patients’ median pain score was 5 (range, 2-7), and their median fatigue score was 4 (range, 3-7). According to the Hospital Anxiety and Depression Scale, patients’ median anxiety score was 6 (range, 4-8), and their median depression score was 6 (range, 4-9).

The intervention

The investigators randomly assigned patients to watch different videos showing doctor-patient interactions with and without computer use. The team had filmed 4 short videos that featured actors playing the parts of doctor and patient.

All study participants were blinded to the hypothesis of the study. The actors were carefully scripted and used the same gestures, expressions, and other nonverbal communication in each video to minimize bias.

Video 1 involved Doctor A in a face-to-face consultation with just a notepad in hand, and Video 2 involved Doctor A in a consultation using a computer.

Video 3 involved Doctor B in a face-to-face consultation with just a notepad in hand, and Video 4 involved Doctor B in a consultation using a computer.

Doctors A and B looked similar, which was intended to minimize bias.

After viewing their first video, patients completed a validated questionnaire rating the doctor’s communication skills, professionalism, and compassion.

Subsequently, each group was assigned to a video topic (face-to-face or computer) they had not viewed previously featuring the doctor they had not viewed in the first video.

A follow-up questionnaire was given after this round of viewing, and the patients were also asked to rate their overall physician preference.

Results

After the first round of viewing, the patients gave better ratings to doctors (A or B) in the face-to-face videos than in the computer videos. Face-to-face doctors were rated significantly higher for compassion (P=0.0003), communication skills (P=0.0012), and professionalism (P=0.0001).

After patients had watched both videos, doctors in the face-to-face videos still had better scores for compassion, communication, and professionalism (P<0.001 for all).

Most patients (72%) said they preferred the face-to-face consultation, while 8% said they preferred the computer consultation, and 20% said they had no preference.

Dr Haider said a possible explanation for these findings is that patients with serious chronic illnesses might value undivided attention from their physicians, and patients might perceive providers using computers as more distracted or multitasking during visits.

“We know that having a good rapport with patients can be extremely beneficial for their health,” Dr Haider said. “Patients with advanced disease need the cues that come with direct interaction to help them along with their care.”

However, Dr Haider also noted that additional research is needed to confirm these results. And he said perceptions might be different in a younger population with higher computer literacy.

*Data in the abstract differ from the presentation.

Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.

Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.

“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).

PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.

In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.

Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).

Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.

“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.

The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.

Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.

Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.

“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).

PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.

In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.

Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).

Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.

“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.

The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.

Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.

Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.

“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).

PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.

In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.

Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).

Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.

“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.

The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).

The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.

This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.

The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.

The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.

Phase 2 trial

The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.

According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.

The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).

Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.

This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.