Non-Hodgkin Lymphoma

Prescriptions

Credit: CDC

The US Food and Drug Administration (FDA) has granted approval for ibrutinib (Imbruvica) as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM).

The drug is now approved as a single agent for use in all lines of therapy.

This is the fourth indication for ibrutinib, which is also FDA-approved to treat patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients with del 17p, and patients with mantle cell lymphoma.

Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

The latest FDA approval is based on results from a multicenter, phase 2 study in which researchers evaluated the efficacy and tolerability of ibrutinib in 63 patients with previously treated WM.

The response rate, according to an independent review committee, was 62%. Eleven percent of patients had a very good partial response rate, and 51% had a partial response rate.

The median duration of response has not been reached, with a range of 2.8 to 18.8 months.

The most commonly occurring adverse events (>20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.

Six percent of patients discontinued treatment due to adverse events. Events leading to dose reduction occurred in 11% of patients.

For more details, see the full prescribing information.

Prescriptions

Credit: CDC

The US Food and Drug Administration (FDA) has granted approval for ibrutinib (Imbruvica) as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM).

The drug is now approved as a single agent for use in all lines of therapy.

This is the fourth indication for ibrutinib, which is also FDA-approved to treat patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients with del 17p, and patients with mantle cell lymphoma.

Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

The latest FDA approval is based on results from a multicenter, phase 2 study in which researchers evaluated the efficacy and tolerability of ibrutinib in 63 patients with previously treated WM.

The response rate, according to an independent review committee, was 62%. Eleven percent of patients had a very good partial response rate, and 51% had a partial response rate.

The median duration of response has not been reached, with a range of 2.8 to 18.8 months.

The most commonly occurring adverse events (>20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.

Six percent of patients discontinued treatment due to adverse events. Events leading to dose reduction occurred in 11% of patients.

For more details, see the full prescribing information.

Prescriptions

Credit: CDC

The US Food and Drug Administration (FDA) has granted approval for ibrutinib (Imbruvica) as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM).

The drug is now approved as a single agent for use in all lines of therapy.

This is the fourth indication for ibrutinib, which is also FDA-approved to treat patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients with del 17p, and patients with mantle cell lymphoma.

Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

The latest FDA approval is based on results from a multicenter, phase 2 study in which researchers evaluated the efficacy and tolerability of ibrutinib in 63 patients with previously treated WM.

The response rate, according to an independent review committee, was 62%. Eleven percent of patients had a very good partial response rate, and 51% had a partial response rate.

The median duration of response has not been reached, with a range of 2.8 to 18.8 months.

The most commonly occurring adverse events (>20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.

Six percent of patients discontinued treatment due to adverse events. Events leading to dose reduction occurred in 11% of patients.

For more details, see the full prescribing information.

Burkitt lymphoma cells

Credit: Ed Uthman

New research has revealed how Epstein Barr virus (EBV) and other herpes viruses outwit the body’s immune response.

It seems these viruses carry microRNAs (miRNAs) that block the interferon (IFN) response—when immune cells release IFN to prevent viral replication, which often kills or slows the growth of infected host cells.

This appears to explain why patients with EBV-positive lymphomas and other viral cancers may resist treatment with IFN.

Jennifer Cox, a graduate student at the University of Texas Austin, and her colleagues recounted these findings in PNAS.

The team noted that many viruses, including EBV, carry miRNAs they use to hijack natural processes in a host’s cells during an infection.

Viral miRNAs are known to prevent host cell death, promote host cell growth, and dampen the host cell’s viral defenses. However, scientists don’t yet know which viral miRNAs perform which functions.

To gain some insight, Cox and her colleagues screened a library of more than 70 human viral miRNAs. This revealed 3 unrelated miRNAs from distantly related herpes viruses that significantly inhibited IFN signaling.

The 5’ and 3’ derivatives from EBV-encoded miR-BART-18 precursor miRNA and the orthologous precursor miRNA from Rhesus lymphocryptovirus all reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which, as part of the p300-CBP complex, mediates IFN signaling.

When the researchers restored miR-BART-18 to cells infected with an EBV miRNA mutant, they observed a cellular growth advantage upon IFN treatment. And they found that miRNAs from other herpes viruses were able to complement this activity.

The team also showed that blocking miR-BART-18 function in an EBV-positive tumor cell line rendered cells more susceptible to IFN-mediated effects.

“[These findings] could explain the variability seen in the success of previous interferon-based cancer treatments,” Cox said. “While this work does not immediately identify new drugs, the fact that such different tumor viruses have converged on the same strategy makes this an exciting pursuit for future therapies against viral cancers.”

Burkitt lymphoma cells

Credit: Ed Uthman

New research has revealed how Epstein Barr virus (EBV) and other herpes viruses outwit the body’s immune response.

It seems these viruses carry microRNAs (miRNAs) that block the interferon (IFN) response—when immune cells release IFN to prevent viral replication, which often kills or slows the growth of infected host cells.

This appears to explain why patients with EBV-positive lymphomas and other viral cancers may resist treatment with IFN.

Jennifer Cox, a graduate student at the University of Texas Austin, and her colleagues recounted these findings in PNAS.

The team noted that many viruses, including EBV, carry miRNAs they use to hijack natural processes in a host’s cells during an infection.

Viral miRNAs are known to prevent host cell death, promote host cell growth, and dampen the host cell’s viral defenses. However, scientists don’t yet know which viral miRNAs perform which functions.

To gain some insight, Cox and her colleagues screened a library of more than 70 human viral miRNAs. This revealed 3 unrelated miRNAs from distantly related herpes viruses that significantly inhibited IFN signaling.

The 5’ and 3’ derivatives from EBV-encoded miR-BART-18 precursor miRNA and the orthologous precursor miRNA from Rhesus lymphocryptovirus all reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which, as part of the p300-CBP complex, mediates IFN signaling.

When the researchers restored miR-BART-18 to cells infected with an EBV miRNA mutant, they observed a cellular growth advantage upon IFN treatment. And they found that miRNAs from other herpes viruses were able to complement this activity.

The team also showed that blocking miR-BART-18 function in an EBV-positive tumor cell line rendered cells more susceptible to IFN-mediated effects.

“[These findings] could explain the variability seen in the success of previous interferon-based cancer treatments,” Cox said. “While this work does not immediately identify new drugs, the fact that such different tumor viruses have converged on the same strategy makes this an exciting pursuit for future therapies against viral cancers.”

Burkitt lymphoma cells

Credit: Ed Uthman

New research has revealed how Epstein Barr virus (EBV) and other herpes viruses outwit the body’s immune response.

It seems these viruses carry microRNAs (miRNAs) that block the interferon (IFN) response—when immune cells release IFN to prevent viral replication, which often kills or slows the growth of infected host cells.

This appears to explain why patients with EBV-positive lymphomas and other viral cancers may resist treatment with IFN.

Jennifer Cox, a graduate student at the University of Texas Austin, and her colleagues recounted these findings in PNAS.

The team noted that many viruses, including EBV, carry miRNAs they use to hijack natural processes in a host’s cells during an infection.

Viral miRNAs are known to prevent host cell death, promote host cell growth, and dampen the host cell’s viral defenses. However, scientists don’t yet know which viral miRNAs perform which functions.

To gain some insight, Cox and her colleagues screened a library of more than 70 human viral miRNAs. This revealed 3 unrelated miRNAs from distantly related herpes viruses that significantly inhibited IFN signaling.

The 5’ and 3’ derivatives from EBV-encoded miR-BART-18 precursor miRNA and the orthologous precursor miRNA from Rhesus lymphocryptovirus all reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which, as part of the p300-CBP complex, mediates IFN signaling.

When the researchers restored miR-BART-18 to cells infected with an EBV miRNA mutant, they observed a cellular growth advantage upon IFN treatment. And they found that miRNAs from other herpes viruses were able to complement this activity.

The team also showed that blocking miR-BART-18 function in an EBV-positive tumor cell line rendered cells more susceptible to IFN-mediated effects.

“[These findings] could explain the variability seen in the success of previous interferon-based cancer treatments,” Cox said. “While this work does not immediately identify new drugs, the fact that such different tumor viruses have converged on the same strategy makes this an exciting pursuit for future therapies against viral cancers.”

Doctor consults with patient

Credit: NIH

The “transformation” of treatment for chronic lymphocytic leukemia (CLL) is the “Advance of the Year” for 2015, according to a report by the American Society of Clinical Oncology (ASCO).

The report said 4 therapies that were recently approved in the US fill a major unmet need for CLL patients—obinutuzumab and ofatumumab for patients with previously untreated CLL and idelalisib and ibrutinib for patients with relapsed or refractory CLL.

“For many older patients, especially, these drugs essentially offer the first chance at effective treatment, since the side effects of earlier options were simply too toxic for many to handle,” said Gregory Masters, MD, ASCO expert and co-executive editor of the report.

The report, “Clinical Cancer Advances 2015: ASCO’s Annual Report on Progress Against Cancer,” is available in the Journal of Clinical Oncology and on ASCO’s cancer research advocacy website, CancerProgress.net.

The report was developed under the direction of an 18-person editorial board of experts from a wide range of oncology specialties. It features:

• The top cancer research advances of the past year: Identifying major trends in cancer prevention and screening, treatment, quality of life, survivorship, and tumor biology
• A Decade in Review: Recounting improvements in cancer care since the first issue of Clinical Cancer Advances
• The 10-Year Horizon: Previewing trends likely to shape the next decade of cancer care, including genomic technology, nanomedicine, and health information technologies
• Progress in Rare Cancers: Highlighting promising early achievements in treating certain uncommon but devastating cancers.

“This has truly been a banner year for CLL and for clinical cancer research as a whole,” said ASCO President Peter P. Yu, MD. “Advances in cancer prevention and care, especially those in precision medicine, are offering stunning new possibilities for patients.”

Doctor consults with patient

Credit: NIH

The “transformation” of treatment for chronic lymphocytic leukemia (CLL) is the “Advance of the Year” for 2015, according to a report by the American Society of Clinical Oncology (ASCO).

The report said 4 therapies that were recently approved in the US fill a major unmet need for CLL patients—obinutuzumab and ofatumumab for patients with previously untreated CLL and idelalisib and ibrutinib for patients with relapsed or refractory CLL.

“For many older patients, especially, these drugs essentially offer the first chance at effective treatment, since the side effects of earlier options were simply too toxic for many to handle,” said Gregory Masters, MD, ASCO expert and co-executive editor of the report.

The report, “Clinical Cancer Advances 2015: ASCO’s Annual Report on Progress Against Cancer,” is available in the Journal of Clinical Oncology and on ASCO’s cancer research advocacy website, CancerProgress.net.

The report was developed under the direction of an 18-person editorial board of experts from a wide range of oncology specialties. It features:

• The top cancer research advances of the past year: Identifying major trends in cancer prevention and screening, treatment, quality of life, survivorship, and tumor biology
• A Decade in Review: Recounting improvements in cancer care since the first issue of Clinical Cancer Advances
• The 10-Year Horizon: Previewing trends likely to shape the next decade of cancer care, including genomic technology, nanomedicine, and health information technologies
• Progress in Rare Cancers: Highlighting promising early achievements in treating certain uncommon but devastating cancers.

“This has truly been a banner year for CLL and for clinical cancer research as a whole,” said ASCO President Peter P. Yu, MD. “Advances in cancer prevention and care, especially those in precision medicine, are offering stunning new possibilities for patients.”

Doctor consults with patient

Credit: NIH

The “transformation” of treatment for chronic lymphocytic leukemia (CLL) is the “Advance of the Year” for 2015, according to a report by the American Society of Clinical Oncology (ASCO).

The report said 4 therapies that were recently approved in the US fill a major unmet need for CLL patients—obinutuzumab and ofatumumab for patients with previously untreated CLL and idelalisib and ibrutinib for patients with relapsed or refractory CLL.

“For many older patients, especially, these drugs essentially offer the first chance at effective treatment, since the side effects of earlier options were simply too toxic for many to handle,” said Gregory Masters, MD, ASCO expert and co-executive editor of the report.

The report, “Clinical Cancer Advances 2015: ASCO’s Annual Report on Progress Against Cancer,” is available in the Journal of Clinical Oncology and on ASCO’s cancer research advocacy website, CancerProgress.net.

The report was developed under the direction of an 18-person editorial board of experts from a wide range of oncology specialties. It features:

• The top cancer research advances of the past year: Identifying major trends in cancer prevention and screening, treatment, quality of life, survivorship, and tumor biology
• A Decade in Review: Recounting improvements in cancer care since the first issue of Clinical Cancer Advances
• The 10-Year Horizon: Previewing trends likely to shape the next decade of cancer care, including genomic technology, nanomedicine, and health information technologies
• Progress in Rare Cancers: Highlighting promising early achievements in treating certain uncommon but devastating cancers.

“This has truly been a banner year for CLL and for clinical cancer research as a whole,” said ASCO President Peter P. Yu, MD. “Advances in cancer prevention and care, especially those in precision medicine, are offering stunning new possibilities for patients.”

Prescription drugs

Credit: CDC

Several hematology drugs approved by the US Food and Drug Administration (FDA) have recently undergone label changes to reflect newly reported adverse events.

Changes have been made to the labels for the JAK1/2 inhibitor ruxolitinib (Jakafi), the anti-CD20 monoclonal antibody obinutuzumab (Gazyva), the factor Xa inhibitor rivaroxaban (Xarelto), and the hematopoietic stem cell mobilizer plerixafor (Mozobil).

Plerixafor

Plerixafor is FDA-approved for use in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma.

The product’s label was changed to include a new entry under the “Adverse Reactions” heading. Postmarketing experience suggested the drug may cause abnormal dreams and nightmares.

Rivaroxaban

Rivaroxaban is a factor Xa inhibitor that’s FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT and PE, and to prevent DVT, which may lead to PE, in patients undergoing knee or hip replacement surgery.

Postmarketing experience has led to two changes to the “Adverse Reactions” section of rivaroxaban’s label. Thrombocytopenia has been added as an adverse reaction, and the term “cytolytic hepatitis” has been replaced with “hepatitis (including hepatocellular injury).”

Obinutuzumab

Obinutuzumab is a CD20-directed cytolytic antibody that is FDA-approved in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

The “Warnings and Precautions” section of obinutuzumab’s label has been changed to reflect that fatal infections have been reported in patients who received the drug.

The label has also been changed to coincide with changes in trial data. The label now states that obinutuzumab caused grade 3 or 4 neutropenia in 33% of patients and grade 3 or 4 thrombocytopenia in 10% of patients.

Ruxolitinib

Ruxolitinib is a JAK1/JAK2 inhibitor that’s FDA-approved to treat patients with polycythemia vera (PV) who cannot tolerate or don’t respond to hydroxyurea, as well as patients with intermediate or high-risk myelofibrosis.

Ruxolitinib’s label now includes a warning that symptoms of myeloproliferative neoplasms may return about a week after discontinuing treatment. The label also advises healthcare professionals to discourage patients form interrupting or discontinuing ruxolitinib without consulting their physician.

In addition, a warning about the risk of non-melanoma skin cancer associated with ruxolitinib, as well as advice for informing patients of this risk, have been added to ruxolitinib’s label.

The label has undergone significant changes in sections 6.1, “Clinical Trials Experience in Myelofibrosis” and 6.2 “Clinical Trial Experience in Polycythemia Vera.” It now includes additional information on the risk of thrombocytopenia, anemia, and neutropenia.

Under the “Special Populations” heading, recommendations were added to reduce the drug’s dose in patients with PV and moderate or severe renal impairment, as well as PV patients with hepatic impairment.

Prescription drugs

Credit: CDC

Several hematology drugs approved by the US Food and Drug Administration (FDA) have recently undergone label changes to reflect newly reported adverse events.

Changes have been made to the labels for the JAK1/2 inhibitor ruxolitinib (Jakafi), the anti-CD20 monoclonal antibody obinutuzumab (Gazyva), the factor Xa inhibitor rivaroxaban (Xarelto), and the hematopoietic stem cell mobilizer plerixafor (Mozobil).

Plerixafor

Plerixafor is FDA-approved for use in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma.

The product’s label was changed to include a new entry under the “Adverse Reactions” heading. Postmarketing experience suggested the drug may cause abnormal dreams and nightmares.

Rivaroxaban

Rivaroxaban is a factor Xa inhibitor that’s FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT and PE, and to prevent DVT, which may lead to PE, in patients undergoing knee or hip replacement surgery.

Postmarketing experience has led to two changes to the “Adverse Reactions” section of rivaroxaban’s label. Thrombocytopenia has been added as an adverse reaction, and the term “cytolytic hepatitis” has been replaced with “hepatitis (including hepatocellular injury).”

Obinutuzumab

Obinutuzumab is a CD20-directed cytolytic antibody that is FDA-approved in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

The “Warnings and Precautions” section of obinutuzumab’s label has been changed to reflect that fatal infections have been reported in patients who received the drug.

The label has also been changed to coincide with changes in trial data. The label now states that obinutuzumab caused grade 3 or 4 neutropenia in 33% of patients and grade 3 or 4 thrombocytopenia in 10% of patients.

Ruxolitinib

Ruxolitinib is a JAK1/JAK2 inhibitor that’s FDA-approved to treat patients with polycythemia vera (PV) who cannot tolerate or don’t respond to hydroxyurea, as well as patients with intermediate or high-risk myelofibrosis.

Ruxolitinib’s label now includes a warning that symptoms of myeloproliferative neoplasms may return about a week after discontinuing treatment. The label also advises healthcare professionals to discourage patients form interrupting or discontinuing ruxolitinib without consulting their physician.

In addition, a warning about the risk of non-melanoma skin cancer associated with ruxolitinib, as well as advice for informing patients of this risk, have been added to ruxolitinib’s label.

The label has undergone significant changes in sections 6.1, “Clinical Trials Experience in Myelofibrosis” and 6.2 “Clinical Trial Experience in Polycythemia Vera.” It now includes additional information on the risk of thrombocytopenia, anemia, and neutropenia.

Under the “Special Populations” heading, recommendations were added to reduce the drug’s dose in patients with PV and moderate or severe renal impairment, as well as PV patients with hepatic impairment.

Prescription drugs

Credit: CDC

Several hematology drugs approved by the US Food and Drug Administration (FDA) have recently undergone label changes to reflect newly reported adverse events.

Changes have been made to the labels for the JAK1/2 inhibitor ruxolitinib (Jakafi), the anti-CD20 monoclonal antibody obinutuzumab (Gazyva), the factor Xa inhibitor rivaroxaban (Xarelto), and the hematopoietic stem cell mobilizer plerixafor (Mozobil).

Plerixafor

Plerixafor is FDA-approved for use in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma.

The product’s label was changed to include a new entry under the “Adverse Reactions” heading. Postmarketing experience suggested the drug may cause abnormal dreams and nightmares.

Rivaroxaban

Rivaroxaban is a factor Xa inhibitor that’s FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT and PE, and to prevent DVT, which may lead to PE, in patients undergoing knee or hip replacement surgery.

Postmarketing experience has led to two changes to the “Adverse Reactions” section of rivaroxaban’s label. Thrombocytopenia has been added as an adverse reaction, and the term “cytolytic hepatitis” has been replaced with “hepatitis (including hepatocellular injury).”

Obinutuzumab

Obinutuzumab is a CD20-directed cytolytic antibody that is FDA-approved in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.

The “Warnings and Precautions” section of obinutuzumab’s label has been changed to reflect that fatal infections have been reported in patients who received the drug.

The label has also been changed to coincide with changes in trial data. The label now states that obinutuzumab caused grade 3 or 4 neutropenia in 33% of patients and grade 3 or 4 thrombocytopenia in 10% of patients.

Ruxolitinib

Ruxolitinib is a JAK1/JAK2 inhibitor that’s FDA-approved to treat patients with polycythemia vera (PV) who cannot tolerate or don’t respond to hydroxyurea, as well as patients with intermediate or high-risk myelofibrosis.

Ruxolitinib’s label now includes a warning that symptoms of myeloproliferative neoplasms may return about a week after discontinuing treatment. The label also advises healthcare professionals to discourage patients form interrupting or discontinuing ruxolitinib without consulting their physician.

In addition, a warning about the risk of non-melanoma skin cancer associated with ruxolitinib, as well as advice for informing patients of this risk, have been added to ruxolitinib’s label.

The label has undergone significant changes in sections 6.1, “Clinical Trials Experience in Myelofibrosis” and 6.2 “Clinical Trial Experience in Polycythemia Vera.” It now includes additional information on the risk of thrombocytopenia, anemia, and neutropenia.

Under the “Special Populations” heading, recommendations were added to reduce the drug’s dose in patients with PV and moderate or severe renal impairment, as well as PV patients with hepatic impairment.

Prescription medications

Credit: Steven Harbour

The National Health Service (NHS) has increased the budget for England’s Cancer Drugs Fund (CDF) and  added a new drug to treat 2 hematologic malignancies, but 5 other blood cancer drugs will be removed from the fund in March.

The budget for the CDF will grow from £200 million in 2013/14 to £280 million in 2014/15.

However, 16 drugs (for 25 different indications) will no longer be offered through the fund as of March 12, 2015.

Still, the NHS said it has taken steps to ensure patients can receive appropriate treatment.

Review leads to cuts

A national panel of oncologists, pharmacists, and patient representatives independently reviewed the drug indications currently available through the CDF, plus new applications.

They evaluated the clinical benefit, survival, quality of life, toxicity, and safety associated with each treatment, as well as the level of unmet need and the median cost per patient. In cases where the high cost of a drug would lead to its exclusion from CDF, manufacturers were given an opportunity to reduce prices.

The result of the review is that 59 of the 84 most effective currently approved indications of drugs will rollover into the CDF next year, creating room for new drug indications that will be funded for the first time.

These are panitumumab for bowel cancer, ibrutinib for mantle cell lymphoma, and ibrutinib for chronic lymphocytic leukemia.

However, 16 drugs, including 5 blood cancer drugs—bendamustine, bortezomib, bosutinib, dasatinib, and ofatumumab—will no longer be offered through the CDF.

Following these changes, the NHS will put 4 measures in place to ensure patients can receive appropriate treatment. First, any patient currently receiving a drug through the CDF will continue to receive it, regardless of whether it remains in the CDF.

Second, drugs that are the only therapy for the cancer in question will remain available through the CDF. Third, if the CDF panel removes a drug for a particular indication, some patients may instead be able to receive it in another line of therapy or receive an alternative CDF-approved drug.

And finally, clinicians can apply for their patient to receive a drug not available through the CDF on an exceptional basis.

Cuts to blood cancer drugs

The full list of cuts to the CDF is available on the NHS website, but the following list includes all drugs for hematologic malignancies that will no longer be available. These drugs will still be available for other indications, however.

1. Bendamustine for the treatment of low-grade lymphoma that is refractory to rituximab alone or in combination.
2. Bortezomib for the treatment of:

   • relapsed/refractory mantle cell lymphoma after 1 or more prior chemotherapies or stem cell transplant
   • relapsed multiple myeloma patients with a previous partial response or complete response of 6 months or more with bortezomib
   • relapsed Waldenstrom’s macroglobulinemia patients who received previous treatment with alkylating agents and purine analogues.

3. Bosutinib for the treatment of:

   • blast crisis chronic myeloid leukemia (CML) that is refractory to nilotinib or dasatinib if dasatinib was accessed via a clinical trial or via its current approved CDF indication
   • blast crisis CML where there is treatment intolerance, specifically, significant intolerance to dasatinib (grade 3 or 4 adverse events) if dasatinib was accessed via its current approved CDF indication.

4. Dasatinib for the treatment of lymphoid, blast crisis CML that is refractory to, significantly intolerant of, or resistant to prior therapy including imatinib (grade 3 or 4 adverse events); also when used as the 2nd- or 3rd-line treatment.
5. Ofatumumab for the treatment of CML as the 2nd- or 3rd-line indication and if the patient is refractory to treatment with fludarabine in combination and/or alemtuzumab or if treatment with fludarabine in combination and/or alemtuzumab is contraindicated.

More about the CDF and the NHS

The CDF—set up in 2010 and currently due to run until March 2016—is money the government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. Most cancer drugs are routinely funded outside of the CDF.

NHS England said it is working with cancer charities, the pharmaceutical industry, and NICE to create a sustainable model for the commissioning of chemotherapy. The agency has also updated its procedures for evaluating drugs in the CDF, in an effort to ensure sustainability.

In addition, NHS England has set up an appeals process by which pharmaceutical companies can challenge the decision-making process.

And a newly assembled national taskforce, headed by Harpal Kumar, chief executive of Cancer Research UK, is set to produce a refreshed, 5-year cancer plan for the NHS.

Prescription medications

Credit: Steven Harbour

The National Health Service (NHS) has increased the budget for England’s Cancer Drugs Fund (CDF) and  added a new drug to treat 2 hematologic malignancies, but 5 other blood cancer drugs will be removed from the fund in March.

The budget for the CDF will grow from £200 million in 2013/14 to £280 million in 2014/15.

However, 16 drugs (for 25 different indications) will no longer be offered through the fund as of March 12, 2015.

Still, the NHS said it has taken steps to ensure patients can receive appropriate treatment.

Review leads to cuts

A national panel of oncologists, pharmacists, and patient representatives independently reviewed the drug indications currently available through the CDF, plus new applications.

They evaluated the clinical benefit, survival, quality of life, toxicity, and safety associated with each treatment, as well as the level of unmet need and the median cost per patient. In cases where the high cost of a drug would lead to its exclusion from CDF, manufacturers were given an opportunity to reduce prices.

The result of the review is that 59 of the 84 most effective currently approved indications of drugs will rollover into the CDF next year, creating room for new drug indications that will be funded for the first time.

These are panitumumab for bowel cancer, ibrutinib for mantle cell lymphoma, and ibrutinib for chronic lymphocytic leukemia.

However, 16 drugs, including 5 blood cancer drugs—bendamustine, bortezomib, bosutinib, dasatinib, and ofatumumab—will no longer be offered through the CDF.

Following these changes, the NHS will put 4 measures in place to ensure patients can receive appropriate treatment. First, any patient currently receiving a drug through the CDF will continue to receive it, regardless of whether it remains in the CDF.

Second, drugs that are the only therapy for the cancer in question will remain available through the CDF. Third, if the CDF panel removes a drug for a particular indication, some patients may instead be able to receive it in another line of therapy or receive an alternative CDF-approved drug.

And finally, clinicians can apply for their patient to receive a drug not available through the CDF on an exceptional basis.

Cuts to blood cancer drugs

The full list of cuts to the CDF is available on the NHS website, but the following list includes all drugs for hematologic malignancies that will no longer be available. These drugs will still be available for other indications, however.

1. Bendamustine for the treatment of low-grade lymphoma that is refractory to rituximab alone or in combination.
2. Bortezomib for the treatment of:

   • relapsed/refractory mantle cell lymphoma after 1 or more prior chemotherapies or stem cell transplant
   • relapsed multiple myeloma patients with a previous partial response or complete response of 6 months or more with bortezomib
   • relapsed Waldenstrom’s macroglobulinemia patients who received previous treatment with alkylating agents and purine analogues.

3. Bosutinib for the treatment of:

   • blast crisis chronic myeloid leukemia (CML) that is refractory to nilotinib or dasatinib if dasatinib was accessed via a clinical trial or via its current approved CDF indication
   • blast crisis CML where there is treatment intolerance, specifically, significant intolerance to dasatinib (grade 3 or 4 adverse events) if dasatinib was accessed via its current approved CDF indication.

4. Dasatinib for the treatment of lymphoid, blast crisis CML that is refractory to, significantly intolerant of, or resistant to prior therapy including imatinib (grade 3 or 4 adverse events); also when used as the 2nd- or 3rd-line treatment.
5. Ofatumumab for the treatment of CML as the 2nd- or 3rd-line indication and if the patient is refractory to treatment with fludarabine in combination and/or alemtuzumab or if treatment with fludarabine in combination and/or alemtuzumab is contraindicated.

More about the CDF and the NHS

The CDF—set up in 2010 and currently due to run until March 2016—is money the government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. Most cancer drugs are routinely funded outside of the CDF.

NHS England said it is working with cancer charities, the pharmaceutical industry, and NICE to create a sustainable model for the commissioning of chemotherapy. The agency has also updated its procedures for evaluating drugs in the CDF, in an effort to ensure sustainability.

In addition, NHS England has set up an appeals process by which pharmaceutical companies can challenge the decision-making process.

And a newly assembled national taskforce, headed by Harpal Kumar, chief executive of Cancer Research UK, is set to produce a refreshed, 5-year cancer plan for the NHS.

Prescription medications

Credit: Steven Harbour

The National Health Service (NHS) has increased the budget for England’s Cancer Drugs Fund (CDF) and  added a new drug to treat 2 hematologic malignancies, but 5 other blood cancer drugs will be removed from the fund in March.

The budget for the CDF will grow from £200 million in 2013/14 to £280 million in 2014/15.

However, 16 drugs (for 25 different indications) will no longer be offered through the fund as of March 12, 2015.

Still, the NHS said it has taken steps to ensure patients can receive appropriate treatment.

Review leads to cuts

A national panel of oncologists, pharmacists, and patient representatives independently reviewed the drug indications currently available through the CDF, plus new applications.

They evaluated the clinical benefit, survival, quality of life, toxicity, and safety associated with each treatment, as well as the level of unmet need and the median cost per patient. In cases where the high cost of a drug would lead to its exclusion from CDF, manufacturers were given an opportunity to reduce prices.

The result of the review is that 59 of the 84 most effective currently approved indications of drugs will rollover into the CDF next year, creating room for new drug indications that will be funded for the first time.

These are panitumumab for bowel cancer, ibrutinib for mantle cell lymphoma, and ibrutinib for chronic lymphocytic leukemia.

However, 16 drugs, including 5 blood cancer drugs—bendamustine, bortezomib, bosutinib, dasatinib, and ofatumumab—will no longer be offered through the CDF.

Following these changes, the NHS will put 4 measures in place to ensure patients can receive appropriate treatment. First, any patient currently receiving a drug through the CDF will continue to receive it, regardless of whether it remains in the CDF.

Second, drugs that are the only therapy for the cancer in question will remain available through the CDF. Third, if the CDF panel removes a drug for a particular indication, some patients may instead be able to receive it in another line of therapy or receive an alternative CDF-approved drug.

And finally, clinicians can apply for their patient to receive a drug not available through the CDF on an exceptional basis.

Cuts to blood cancer drugs

The full list of cuts to the CDF is available on the NHS website, but the following list includes all drugs for hematologic malignancies that will no longer be available. These drugs will still be available for other indications, however.

1. Bendamustine for the treatment of low-grade lymphoma that is refractory to rituximab alone or in combination.
2. Bortezomib for the treatment of:

   • relapsed/refractory mantle cell lymphoma after 1 or more prior chemotherapies or stem cell transplant
   • relapsed multiple myeloma patients with a previous partial response or complete response of 6 months or more with bortezomib
   • relapsed Waldenstrom’s macroglobulinemia patients who received previous treatment with alkylating agents and purine analogues.

3. Bosutinib for the treatment of:

   • blast crisis chronic myeloid leukemia (CML) that is refractory to nilotinib or dasatinib if dasatinib was accessed via a clinical trial or via its current approved CDF indication
   • blast crisis CML where there is treatment intolerance, specifically, significant intolerance to dasatinib (grade 3 or 4 adverse events) if dasatinib was accessed via its current approved CDF indication.

4. Dasatinib for the treatment of lymphoid, blast crisis CML that is refractory to, significantly intolerant of, or resistant to prior therapy including imatinib (grade 3 or 4 adverse events); also when used as the 2nd- or 3rd-line treatment.
5. Ofatumumab for the treatment of CML as the 2nd- or 3rd-line indication and if the patient is refractory to treatment with fludarabine in combination and/or alemtuzumab or if treatment with fludarabine in combination and/or alemtuzumab is contraindicated.

More about the CDF and the NHS

The CDF—set up in 2010 and currently due to run until March 2016—is money the government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. Most cancer drugs are routinely funded outside of the CDF.

NHS England said it is working with cancer charities, the pharmaceutical industry, and NICE to create a sustainable model for the commissioning of chemotherapy. The agency has also updated its procedures for evaluating drugs in the CDF, in an effort to ensure sustainability.

In addition, NHS England has set up an appeals process by which pharmaceutical companies can challenge the decision-making process.

And a newly assembled national taskforce, headed by Harpal Kumar, chief executive of Cancer Research UK, is set to produce a refreshed, 5-year cancer plan for the NHS.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to SGX301 as a first-line treatment for cutaneous T-cell lymphoma (CTCL).

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is set to begin in the first half of this year. In addition to its new fast track status, SGX301 also has orphan designation from the FDA.

About fast track designation

The FDA grants fast track designation to a drug that is intended to treat a serious or life-threatening condition and that demonstrates the potential to address an unmet medical need for the condition.

Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, Soligenix, Inc., the company developing SGX301, is eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, allowing the FDA to review sections of the NDA prior to receiving the complete submission.

Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately 6 months.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to SGX301 as a first-line treatment for cutaneous T-cell lymphoma (CTCL).

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is set to begin in the first half of this year. In addition to its new fast track status, SGX301 also has orphan designation from the FDA.

About fast track designation

The FDA grants fast track designation to a drug that is intended to treat a serious or life-threatening condition and that demonstrates the potential to address an unmet medical need for the condition.

Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, Soligenix, Inc., the company developing SGX301, is eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, allowing the FDA to review sections of the NDA prior to receiving the complete submission.

Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately 6 months.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to SGX301 as a first-line treatment for cutaneous T-cell lymphoma (CTCL).

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is set to begin in the first half of this year. In addition to its new fast track status, SGX301 also has orphan designation from the FDA.

About fast track designation

The FDA grants fast track designation to a drug that is intended to treat a serious or life-threatening condition and that demonstrates the potential to address an unmet medical need for the condition.

Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, Soligenix, Inc., the company developing SGX301, is eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, allowing the FDA to review sections of the NDA prior to receiving the complete submission.

Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately 6 months.

Blood collection

Credit: Charles Haymond

The European Commission has granted KTE-C19, a chimeric antigen receptor (CAR) T-cell therapy, orphan designation to treat patients with diffuse large B-cell lymphoma (DLBCL) in the European Union (EU).

To create KTE-C19, a patient’s T cells are genetically modified using a gammaretroviral vector to express a CAR designed to target CD19, a protein expressed on B cells.

The product received orphan designation to treat DLBCL in the US last March.

“We are pleased with the approval of orphan drug designation for KTE-C19 in the EU, another important milestone for Kite Pharma and for the progress of our lead program,” said Arie Belldegrun, MD, President and CEO of Kite Pharma, Inc., the company developing KTE-C19.

Orphan designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 persons in the EU, and where no satisfactory treatment is available.

In addition to a 10-year period of marketing exclusivity in the EU after product approval, orphan drug designation provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase, and direct access to the centralized authorization procedure.

KTE-C19 in DLBCL

In a study published in the Journal of Clinical Oncology last year, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Of the 7 patients with chemotherapy-refractory DLBCL, 4 achieved a complete response to treatment, 2 achieved a partial response, and 1 had stable disease. Three of the complete responses were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

In the entire patient population, KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

For more information on KTE-C19, visit Kite Pharma’s website.

Blood collection

Credit: Charles Haymond

The European Commission has granted KTE-C19, a chimeric antigen receptor (CAR) T-cell therapy, orphan designation to treat patients with diffuse large B-cell lymphoma (DLBCL) in the European Union (EU).

To create KTE-C19, a patient’s T cells are genetically modified using a gammaretroviral vector to express a CAR designed to target CD19, a protein expressed on B cells.

The product received orphan designation to treat DLBCL in the US last March.

“We are pleased with the approval of orphan drug designation for KTE-C19 in the EU, another important milestone for Kite Pharma and for the progress of our lead program,” said Arie Belldegrun, MD, President and CEO of Kite Pharma, Inc., the company developing KTE-C19.

Orphan designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 persons in the EU, and where no satisfactory treatment is available.

In addition to a 10-year period of marketing exclusivity in the EU after product approval, orphan drug designation provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase, and direct access to the centralized authorization procedure.

KTE-C19 in DLBCL

In a study published in the Journal of Clinical Oncology last year, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Of the 7 patients with chemotherapy-refractory DLBCL, 4 achieved a complete response to treatment, 2 achieved a partial response, and 1 had stable disease. Three of the complete responses were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

In the entire patient population, KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

For more information on KTE-C19, visit Kite Pharma’s website.

Blood collection

Credit: Charles Haymond

The European Commission has granted KTE-C19, a chimeric antigen receptor (CAR) T-cell therapy, orphan designation to treat patients with diffuse large B-cell lymphoma (DLBCL) in the European Union (EU).

To create KTE-C19, a patient’s T cells are genetically modified using a gammaretroviral vector to express a CAR designed to target CD19, a protein expressed on B cells.

The product received orphan designation to treat DLBCL in the US last March.

“We are pleased with the approval of orphan drug designation for KTE-C19 in the EU, another important milestone for Kite Pharma and for the progress of our lead program,” said Arie Belldegrun, MD, President and CEO of Kite Pharma, Inc., the company developing KTE-C19.

Orphan designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 persons in the EU, and where no satisfactory treatment is available.

In addition to a 10-year period of marketing exclusivity in the EU after product approval, orphan drug designation provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase, and direct access to the centralized authorization procedure.

KTE-C19 in DLBCL

In a study published in the Journal of Clinical Oncology last year, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Of the 7 patients with chemotherapy-refractory DLBCL, 4 achieved a complete response to treatment, 2 achieved a partial response, and 1 had stable disease. Three of the complete responses were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

In the entire patient population, KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

For more information on KTE-C19, visit Kite Pharma’s website.

HIV budding from

a cultured lymphocyte

Credit: CDC

SAN FRANCISCO—Patients with HIV-related lymphoma (HRL) should not be excluded from clinical trials of autologous stem cell transplant (ASCT) due to their HIV status, new research suggests.

Investigators found no significant difference in rates of treatment failure, disease progression, or survival between transplant-treated historical controls who had lymphoma but not HIV and patients with HRL who received the modified BEAM regimen followed by ASCT on a phase 2 trial.

This suggests patients with chemotherapy-sensitive, relapsed/refractory HRL can be treated successfully with the modified BEAM regimen, said study investigator Joseph Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.

“Patients with treatment-responsive HIV infection and HIV-related lymphoma should be considered candidates for autologous transplant if they meet standard transplant criteria,” he added. “And we would argue that exclusion from clinical trials on the basis of HIV infection alone is no longer justified.”

Dr Alvarnas presented this viewpoint and the research to support it at the 2014 ASH Annual Meeting as abstract 674.

The trial enrolled 43 patients with treatable HIV-1 infection, adequate organ function, and aggressive lymphoma. Three patients were excluded because they could not undergo transplant due to lymphoma progression.

Of the 40 remaining patients, 5 were female, and their median age was 46.9 years (range, 22.5-62.2). They had diffuse large B-cell lymphoma (n=16), plasmablastic lymphoma (n=2), Burkitt/Burkitt-like lymphoma (n=7), and Hodgkin lymphoma (n=15).

The pre-ASCT HIV viral load was undetectable in 31 patients. In the patients with detectable HIV, the median viral load pre-ASCT was 84 copies/μL (range, 50-17,455). The median CD4 count was 250.5/µL (range, 39-797).

Before transplant, 30 patients (75%) were in complete remission, 8 (20%) were in partial remission, and 2 (5%) had relapsed/progressive disease.

The patients underwent ASCT after conditioning with the modified BEAM regimen—carmustine at 300 mg/m² (day -6), etoposide at 100 mg/m² twice daily (days -5 to -2), cytarabine at 100 mg/m² (days -5 to -2), and melphalan at 140 mg/m² (day -1).

Combination antiretroviral therapy (cART) was held during the preparative regimen and resumed after the resolution of gastrointestinal toxicity. The investigators switched efavirenz to an alternative agent 2 or more weeks prior to the planned interruption of cART, as the drug has a long half-life. And AZT was prohibited due to its myelosuppressive effects.

Treatment results

The median follow-up was 24 months. At 100 days post-transplant, the investigators assessed 39 patients for response. One patient was not evaluable due to early death.

Thirty-six of the patients (92.3%) were in complete remission, 1 (2.6%) was in partial remission, and 2 (5.1%) had relapsed or progressive disease.

Fifteen patients reported grade 3 or higher toxicities within a year of transplant. Of the 13 unexpected grade 3-5 adverse events (reported in 9 patients), 5 were infection/sepsis, 1 was acute appendicitis, 1 was acute coronary syndrome, 2 were deep vein thromboses, 2 were gastrointestinal toxicities, and 2 were metabolic abnormalities.

Seventeen patients reported at least 1 infectious episode, 42 events in total, 9 of which were severe. Fourteen patients required readmission to the hospital after transplant.

Within a year of transplant, 5 patients had died—3 from recurrent/persistent disease, 1 due to a fungal infection, and 1 from cardiac arrest. Two additional patients died after the 1-year mark—1 of recurrent/persistent disease and 1 of heart failure.

At 12 months, the rate of overall survival was 86.6%, progression-free survival was 82.3%, progression was 12.5%, and non-relapse mortality was 5.2%.

“In order to place this within context, we had the opportunity to compare our patient experience with 151 matched controls [without HIV] from CIBMTR,” Dr Alvarnas said. “Ninety-three percent of these patients were actually transplanted within 2 years so that they were the time-concordant group, and they were matched for performance score, disease, and disease stage.”

The investigators found no significant difference between their patient group and the HIV-free controls with regard to overall mortality (P=0.56), treatment failure (P=0.10), progression (P=0.06), and treatment-related mortality (P=0.97).

Likewise, there was no significant difference in overall survival between the HRL patients and controls—86.6% and 87.7%, respectively (P=0.56). And the same was true of progression-free survival—82.3% and 69.5%, respectively (P=0.10).

HIV budding from

a cultured lymphocyte

Credit: CDC

SAN FRANCISCO—Patients with HIV-related lymphoma (HRL) should not be excluded from clinical trials of autologous stem cell transplant (ASCT) due to their HIV status, new research suggests.

Investigators found no significant difference in rates of treatment failure, disease progression, or survival between transplant-treated historical controls who had lymphoma but not HIV and patients with HRL who received the modified BEAM regimen followed by ASCT on a phase 2 trial.

This suggests patients with chemotherapy-sensitive, relapsed/refractory HRL can be treated successfully with the modified BEAM regimen, said study investigator Joseph Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.

“Patients with treatment-responsive HIV infection and HIV-related lymphoma should be considered candidates for autologous transplant if they meet standard transplant criteria,” he added. “And we would argue that exclusion from clinical trials on the basis of HIV infection alone is no longer justified.”

Dr Alvarnas presented this viewpoint and the research to support it at the 2014 ASH Annual Meeting as abstract 674.

The trial enrolled 43 patients with treatable HIV-1 infection, adequate organ function, and aggressive lymphoma. Three patients were excluded because they could not undergo transplant due to lymphoma progression.

Of the 40 remaining patients, 5 were female, and their median age was 46.9 years (range, 22.5-62.2). They had diffuse large B-cell lymphoma (n=16), plasmablastic lymphoma (n=2), Burkitt/Burkitt-like lymphoma (n=7), and Hodgkin lymphoma (n=15).

The pre-ASCT HIV viral load was undetectable in 31 patients. In the patients with detectable HIV, the median viral load pre-ASCT was 84 copies/μL (range, 50-17,455). The median CD4 count was 250.5/µL (range, 39-797).

Before transplant, 30 patients (75%) were in complete remission, 8 (20%) were in partial remission, and 2 (5%) had relapsed/progressive disease.

The patients underwent ASCT after conditioning with the modified BEAM regimen—carmustine at 300 mg/m² (day -6), etoposide at 100 mg/m² twice daily (days -5 to -2), cytarabine at 100 mg/m² (days -5 to -2), and melphalan at 140 mg/m² (day -1).

Combination antiretroviral therapy (cART) was held during the preparative regimen and resumed after the resolution of gastrointestinal toxicity. The investigators switched efavirenz to an alternative agent 2 or more weeks prior to the planned interruption of cART, as the drug has a long half-life. And AZT was prohibited due to its myelosuppressive effects.

Treatment results

The median follow-up was 24 months. At 100 days post-transplant, the investigators assessed 39 patients for response. One patient was not evaluable due to early death.

Thirty-six of the patients (92.3%) were in complete remission, 1 (2.6%) was in partial remission, and 2 (5.1%) had relapsed or progressive disease.

Fifteen patients reported grade 3 or higher toxicities within a year of transplant. Of the 13 unexpected grade 3-5 adverse events (reported in 9 patients), 5 were infection/sepsis, 1 was acute appendicitis, 1 was acute coronary syndrome, 2 were deep vein thromboses, 2 were gastrointestinal toxicities, and 2 were metabolic abnormalities.

Seventeen patients reported at least 1 infectious episode, 42 events in total, 9 of which were severe. Fourteen patients required readmission to the hospital after transplant.

Within a year of transplant, 5 patients had died—3 from recurrent/persistent disease, 1 due to a fungal infection, and 1 from cardiac arrest. Two additional patients died after the 1-year mark—1 of recurrent/persistent disease and 1 of heart failure.

At 12 months, the rate of overall survival was 86.6%, progression-free survival was 82.3%, progression was 12.5%, and non-relapse mortality was 5.2%.

“In order to place this within context, we had the opportunity to compare our patient experience with 151 matched controls [without HIV] from CIBMTR,” Dr Alvarnas said. “Ninety-three percent of these patients were actually transplanted within 2 years so that they were the time-concordant group, and they were matched for performance score, disease, and disease stage.”

The investigators found no significant difference between their patient group and the HIV-free controls with regard to overall mortality (P=0.56), treatment failure (P=0.10), progression (P=0.06), and treatment-related mortality (P=0.97).

Likewise, there was no significant difference in overall survival between the HRL patients and controls—86.6% and 87.7%, respectively (P=0.56). And the same was true of progression-free survival—82.3% and 69.5%, respectively (P=0.10).

HIV budding from

a cultured lymphocyte

Credit: CDC

SAN FRANCISCO—Patients with HIV-related lymphoma (HRL) should not be excluded from clinical trials of autologous stem cell transplant (ASCT) due to their HIV status, new research suggests.

Investigators found no significant difference in rates of treatment failure, disease progression, or survival between transplant-treated historical controls who had lymphoma but not HIV and patients with HRL who received the modified BEAM regimen followed by ASCT on a phase 2 trial.

This suggests patients with chemotherapy-sensitive, relapsed/refractory HRL can be treated successfully with the modified BEAM regimen, said study investigator Joseph Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.

“Patients with treatment-responsive HIV infection and HIV-related lymphoma should be considered candidates for autologous transplant if they meet standard transplant criteria,” he added. “And we would argue that exclusion from clinical trials on the basis of HIV infection alone is no longer justified.”

Dr Alvarnas presented this viewpoint and the research to support it at the 2014 ASH Annual Meeting as abstract 674.

The trial enrolled 43 patients with treatable HIV-1 infection, adequate organ function, and aggressive lymphoma. Three patients were excluded because they could not undergo transplant due to lymphoma progression.

Of the 40 remaining patients, 5 were female, and their median age was 46.9 years (range, 22.5-62.2). They had diffuse large B-cell lymphoma (n=16), plasmablastic lymphoma (n=2), Burkitt/Burkitt-like lymphoma (n=7), and Hodgkin lymphoma (n=15).

The pre-ASCT HIV viral load was undetectable in 31 patients. In the patients with detectable HIV, the median viral load pre-ASCT was 84 copies/μL (range, 50-17,455). The median CD4 count was 250.5/µL (range, 39-797).

Before transplant, 30 patients (75%) were in complete remission, 8 (20%) were in partial remission, and 2 (5%) had relapsed/progressive disease.

The patients underwent ASCT after conditioning with the modified BEAM regimen—carmustine at 300 mg/m² (day -6), etoposide at 100 mg/m² twice daily (days -5 to -2), cytarabine at 100 mg/m² (days -5 to -2), and melphalan at 140 mg/m² (day -1).

Combination antiretroviral therapy (cART) was held during the preparative regimen and resumed after the resolution of gastrointestinal toxicity. The investigators switched efavirenz to an alternative agent 2 or more weeks prior to the planned interruption of cART, as the drug has a long half-life. And AZT was prohibited due to its myelosuppressive effects.

Treatment results

The median follow-up was 24 months. At 100 days post-transplant, the investigators assessed 39 patients for response. One patient was not evaluable due to early death.

Thirty-six of the patients (92.3%) were in complete remission, 1 (2.6%) was in partial remission, and 2 (5.1%) had relapsed or progressive disease.

Fifteen patients reported grade 3 or higher toxicities within a year of transplant. Of the 13 unexpected grade 3-5 adverse events (reported in 9 patients), 5 were infection/sepsis, 1 was acute appendicitis, 1 was acute coronary syndrome, 2 were deep vein thromboses, 2 were gastrointestinal toxicities, and 2 were metabolic abnormalities.

Seventeen patients reported at least 1 infectious episode, 42 events in total, 9 of which were severe. Fourteen patients required readmission to the hospital after transplant.

Within a year of transplant, 5 patients had died—3 from recurrent/persistent disease, 1 due to a fungal infection, and 1 from cardiac arrest. Two additional patients died after the 1-year mark—1 of recurrent/persistent disease and 1 of heart failure.

At 12 months, the rate of overall survival was 86.6%, progression-free survival was 82.3%, progression was 12.5%, and non-relapse mortality was 5.2%.

“In order to place this within context, we had the opportunity to compare our patient experience with 151 matched controls [without HIV] from CIBMTR,” Dr Alvarnas said. “Ninety-three percent of these patients were actually transplanted within 2 years so that they were the time-concordant group, and they were matched for performance score, disease, and disease stage.”

The investigators found no significant difference between their patient group and the HIV-free controls with regard to overall mortality (P=0.56), treatment failure (P=0.10), progression (P=0.06), and treatment-related mortality (P=0.97).

Likewise, there was no significant difference in overall survival between the HRL patients and controls—86.6% and 87.7%, respectively (P=0.56). And the same was true of progression-free survival—82.3% and 69.5%, respectively (P=0.10).

 

 

Monoclonal antibodies

Credit: Linda Bartlett

 

SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.

The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).

But there was no significant difference in the median OS, which was not reached in either treatment arm.

Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.

“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”

“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”

To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.

Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.

The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.

“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”

“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”

“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”

Patient outcomes

The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.

The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).

Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).

However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).

Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.

Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).

There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.

“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.

“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”

*Information in the abstract differs from that presented at the meeting.

 

 

Monoclonal antibodies

Credit: Linda Bartlett

 

SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.

The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).

But there was no significant difference in the median OS, which was not reached in either treatment arm.

Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.

“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”

“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”

To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.

Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.

The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.

“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”

“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”

“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”

Patient outcomes

The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.

The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).

Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).

However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).

Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.

Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).

There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.

“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.

“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”

*Information in the abstract differs from that presented at the meeting.

 

 

Monoclonal antibodies

Credit: Linda Bartlett

 

SAN FRANCISCO—Maintenance therapy with the anti-CD20 monoclonal antibody ofatumumab improves progression-free survival (PFS), but not overall survival (OS), in patients with relapsed chronic lymphocytic leukemia (CLL), according to an interim analysis of the PROLONG study.

The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance (P<0.0001).

But there was no significant difference in the median OS, which was not reached in either treatment arm.

Marinus H.J. van Oers, MD, PhD, of the Academisch Medisch Centrum and HOVON in Amsterdam, The Netherlands, reported these results at the 2014 ASH Annual Meeting (abstract 21*). The study was sponsored by GlaxoSmithKline, makers of ofatumumab.

“[A]s of 2014, still we cannot say that we are able to cure CLL,” Dr van Oers noted. “And CLL is characterized by decreasing response duration with subsequent lines of treatment. In this respect, but also a number of other respects, there are similarities in biological behavior between CLL and follicular lymphoma.”

“There is definitely a role—although it’s somewhat debated—for maintenance treatment in follicular lymphoma. Therefore, it is rational to explore safe and effective maintenance treatment in CLL as well.”

To that end, Dr van Oers and his colleagues compared ofatumumab maintenance to observation in patients who were in remission after induction treatment for relapsed CLL. The team enrolled 474 patients who were in complete or partial remission after their 2nd- or 3rd-line treatment for CLL.

Patients were randomized to observation (n=236) or to receive ofatumumab (n=238) at 300 mg, followed 1 week later by 1000 mg every 8 weeks for up to 2 years. Patients on ofatumumab also received premedication with acetaminophen, antihistamine, and glucocorticoid.

The patients were stratified by the number and type of prior therapy, as well as remission status after induction treatment, and baseline characteristics were similar between the two treatment arms.

“The median age was about 65, and about 30% of patients were older than 70 years,” Dr van Oers noted. “[There was] a male preponderance, as you would expect, and the time since diagnosis was somewhere between 5 and 6 years.”

“Most patients were in [partial response], actually 80%, and most patients had received 2 prior regimens, about 70%. As for prior treatments, 80% of patients had received effective immuno-chemotherapy.”

“In both arms, there were only a few patients with unfavorable cytogenetics—11q and 17p deletion. [As for] β2 microglobulin, two-thirds [of patients in both arms] had low levels. And, in both arms, there were almost twice as many IGVH-mutated as unmutated patients.”

Patient outcomes

The median follow-up was 19.1 months. The study’s primary endpoint was PFS, which was defined as the time from randomization to the date of disease progression or death from any cause.

The median PFS was significantly longer in the ofatumumab arm than in the observation arm, at 29.4 months and 15.2 months, respectively (hazard ratio [HR]=0.50; P<0.0001).

Similarly, the time to the start of patients’ next therapy was significantly longer in the ofatumumab arm than in the in observation arm—a median of 38 months and 31.1 months, respectively (HR=0.66, P=0.108).

However, there was no significant difference in OS, which was not reached in either arm (HR=0.85, P=0.4877).

Adverse events (AEs) occurred in 86% of patients in the ofatumumab arm and 72% of patients in the observation arm (P<0.001). Sixty percent of AEs were considered related to ofatumumab. None of the AEs led to study withdrawal.

Grade 3 or higher AEs occurred in 46% of patients in the ofatumumab arm and 28% in the observation arm. They included neutropenia (24% and 10%, respectively; P<0.001), infections (13% and 8%, respectively), thrombocytopenia (2% and 3%, respectively), and infusion-related reactions (1% and 0%, respectively).

There were 5 deaths in the observation arm—1 due to progression and 4 due to causes other than progression, infection, or secondary malignancy. There were 2 deaths in the ofatumumab arm—1 due to infection/sepsis and 1 due to an “other” cause.

“So based on this planned interim analysis, we can conclude that ofatumumab maintenance in relapsed CLL results in a highly significant and clinically meaningful improvement of progression-free survival,” Dr van Oers said in closing.

“It significantly prolongs time to next treatment, it’s well-tolerated, and it’s associated with an adverse event profile which is quite characteristic of anti-CD20 monoclonal antibodies.”

*Information in the abstract differs from that presented at the meeting.

CLL cells in a blood smear

Credit: Mary Ann Thompson

Single-agent ibrutinib can elicit a high response rate in patients with high-risk chronic lymphocytic leukemia (CLL), results of a phase 2 trial suggest.

The Bruton’s tyrosine kinase inhibitor prompted a 92% objective response rate in patients who had previously untreated or relapsed/refractory CLL with either 17p deletion (del 17p) or tumor protein 53 (TP53) aberrations.

Researchers reported this and other results of the trial in The Lancet Oncology.

“Ibrutinib treatment results observed in CLL patients with del 17p or TP53 aberrations are very encouraging given that these patients have a high relapse rate after chemotherapy and are in need of tolerable, effective, and durable treatment options,” said study author Mohammed Farooqui, DO, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland.

He and his colleagues studied 51 patients in this trial, 35 with previously untreated CLL and 16 with relapsed or refractory CLL. Forty-seven of the patients (92%) had del 17p, and 4 patients carried the TP53 aberration but did not have del 17p.

The study’s primary endpoint was overall response rate after 24 weeks. Secondary endpoints included safety, overall survival, progression-free survival, best response, and nodal response.

The median follow-up for all patients was 24 months (15 months for the previously untreated cohort). At 24 weeks, 48 patients were evaluable for response, assessed according to the modified IWCLL 2008 criteria.

Response rates

At 24 weeks, 92% (n=44) of the 48 evaluable patients achieved an objective response. Fifty percent of all evaluable patients achieved a partial response (n=24)—55% of previously untreated patients (n=18) and 40% of relapsed/refractory patients (n=6).

As for best response, 10% of all patients achieved a complete response (n=5)—12% of previously untreated patients (n=4) and 7% of relapsed/refractory patients (n=1). And 67% of patients had a partial response (n=32)—70% of previously untreated patients (n=23) and 60% of relapsed/refractory patients (n=9).

After 8 weeks on therapy, ibrutinib was associated with a more than 50% mean reduction in tumor burden in the bone marrow (44%), lymph nodes (70%), and spleen (79%). After 24 weeks of therapy, the rates of tumor burden reduction (> 50%) increased to 83%, 93%, and 95%, respectively.

Survival and safety

The estimated progression-free survival at 24 months for all patients on an intention-to-treat basis was 82%. Forty-two of the 51 patients (82%) continued on ibrutinib treatment without disease progression.

The estimated overall survival at 24 months was 80% for all patients—84% for previously untreated patients and 74% for patients with relapsed or refractory disease.

At the final follow-up, 8 (16%) patients had died—5 (10%) from progressive disease, 2 (4%) from infection, and 1 (2%) patient with a sudden, unexplained death that may have been treatment-related.

The most common adverse events (occurring in more than 30% of all patients) potentially related to ibrutinib were arthralgia (59%), diarrhea (51%), rash (47%), nail ridging (43%), bruising (33%), and muscle spasms (31%).

The most frequent grade 3 or 4 hematologic adverse events were neutropenia (24%), anemia (14%), and thrombocytopenia (10%). The most common nonhematologic grade 3 adverse event was pneumonia, which occurred in 3 patients (6%).

Nine patients (18%) discontinued treatment. The reasons for discontinuation included disease progression in 5 patients (10%) and death for 3 patients (6%).

This research was sponsored by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute; Danish Cancer Society; Novo Nordisk Foundation; National Institutes of Health Medical Research Scholars Program; and Pharmacyclics Inc.

Ibrutinib is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

CLL cells in a blood smear

Credit: Mary Ann Thompson

Single-agent ibrutinib can elicit a high response rate in patients with high-risk chronic lymphocytic leukemia (CLL), results of a phase 2 trial suggest.

The Bruton’s tyrosine kinase inhibitor prompted a 92% objective response rate in patients who had previously untreated or relapsed/refractory CLL with either 17p deletion (del 17p) or tumor protein 53 (TP53) aberrations.

Researchers reported this and other results of the trial in The Lancet Oncology.

“Ibrutinib treatment results observed in CLL patients with del 17p or TP53 aberrations are very encouraging given that these patients have a high relapse rate after chemotherapy and are in need of tolerable, effective, and durable treatment options,” said study author Mohammed Farooqui, DO, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland.

He and his colleagues studied 51 patients in this trial, 35 with previously untreated CLL and 16 with relapsed or refractory CLL. Forty-seven of the patients (92%) had del 17p, and 4 patients carried the TP53 aberration but did not have del 17p.

The study’s primary endpoint was overall response rate after 24 weeks. Secondary endpoints included safety, overall survival, progression-free survival, best response, and nodal response.

The median follow-up for all patients was 24 months (15 months for the previously untreated cohort). At 24 weeks, 48 patients were evaluable for response, assessed according to the modified IWCLL 2008 criteria.

Response rates

At 24 weeks, 92% (n=44) of the 48 evaluable patients achieved an objective response. Fifty percent of all evaluable patients achieved a partial response (n=24)—55% of previously untreated patients (n=18) and 40% of relapsed/refractory patients (n=6).

As for best response, 10% of all patients achieved a complete response (n=5)—12% of previously untreated patients (n=4) and 7% of relapsed/refractory patients (n=1). And 67% of patients had a partial response (n=32)—70% of previously untreated patients (n=23) and 60% of relapsed/refractory patients (n=9).

After 8 weeks on therapy, ibrutinib was associated with a more than 50% mean reduction in tumor burden in the bone marrow (44%), lymph nodes (70%), and spleen (79%). After 24 weeks of therapy, the rates of tumor burden reduction (> 50%) increased to 83%, 93%, and 95%, respectively.

Survival and safety

The estimated progression-free survival at 24 months for all patients on an intention-to-treat basis was 82%. Forty-two of the 51 patients (82%) continued on ibrutinib treatment without disease progression.

The estimated overall survival at 24 months was 80% for all patients—84% for previously untreated patients and 74% for patients with relapsed or refractory disease.

At the final follow-up, 8 (16%) patients had died—5 (10%) from progressive disease, 2 (4%) from infection, and 1 (2%) patient with a sudden, unexplained death that may have been treatment-related.

The most common adverse events (occurring in more than 30% of all patients) potentially related to ibrutinib were arthralgia (59%), diarrhea (51%), rash (47%), nail ridging (43%), bruising (33%), and muscle spasms (31%).

The most frequent grade 3 or 4 hematologic adverse events were neutropenia (24%), anemia (14%), and thrombocytopenia (10%). The most common nonhematologic grade 3 adverse event was pneumonia, which occurred in 3 patients (6%).

Nine patients (18%) discontinued treatment. The reasons for discontinuation included disease progression in 5 patients (10%) and death for 3 patients (6%).

This research was sponsored by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute; Danish Cancer Society; Novo Nordisk Foundation; National Institutes of Health Medical Research Scholars Program; and Pharmacyclics Inc.

Ibrutinib is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

CLL cells in a blood smear

Credit: Mary Ann Thompson

Single-agent ibrutinib can elicit a high response rate in patients with high-risk chronic lymphocytic leukemia (CLL), results of a phase 2 trial suggest.

The Bruton’s tyrosine kinase inhibitor prompted a 92% objective response rate in patients who had previously untreated or relapsed/refractory CLL with either 17p deletion (del 17p) or tumor protein 53 (TP53) aberrations.

Researchers reported this and other results of the trial in The Lancet Oncology.

“Ibrutinib treatment results observed in CLL patients with del 17p or TP53 aberrations are very encouraging given that these patients have a high relapse rate after chemotherapy and are in need of tolerable, effective, and durable treatment options,” said study author Mohammed Farooqui, DO, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland.

He and his colleagues studied 51 patients in this trial, 35 with previously untreated CLL and 16 with relapsed or refractory CLL. Forty-seven of the patients (92%) had del 17p, and 4 patients carried the TP53 aberration but did not have del 17p.

The study’s primary endpoint was overall response rate after 24 weeks. Secondary endpoints included safety, overall survival, progression-free survival, best response, and nodal response.

The median follow-up for all patients was 24 months (15 months for the previously untreated cohort). At 24 weeks, 48 patients were evaluable for response, assessed according to the modified IWCLL 2008 criteria.

Response rates

At 24 weeks, 92% (n=44) of the 48 evaluable patients achieved an objective response. Fifty percent of all evaluable patients achieved a partial response (n=24)—55% of previously untreated patients (n=18) and 40% of relapsed/refractory patients (n=6).

As for best response, 10% of all patients achieved a complete response (n=5)—12% of previously untreated patients (n=4) and 7% of relapsed/refractory patients (n=1). And 67% of patients had a partial response (n=32)—70% of previously untreated patients (n=23) and 60% of relapsed/refractory patients (n=9).

After 8 weeks on therapy, ibrutinib was associated with a more than 50% mean reduction in tumor burden in the bone marrow (44%), lymph nodes (70%), and spleen (79%). After 24 weeks of therapy, the rates of tumor burden reduction (> 50%) increased to 83%, 93%, and 95%, respectively.

Survival and safety

The estimated progression-free survival at 24 months for all patients on an intention-to-treat basis was 82%. Forty-two of the 51 patients (82%) continued on ibrutinib treatment without disease progression.

The estimated overall survival at 24 months was 80% for all patients—84% for previously untreated patients and 74% for patients with relapsed or refractory disease.

At the final follow-up, 8 (16%) patients had died—5 (10%) from progressive disease, 2 (4%) from infection, and 1 (2%) patient with a sudden, unexplained death that may have been treatment-related.

The most common adverse events (occurring in more than 30% of all patients) potentially related to ibrutinib were arthralgia (59%), diarrhea (51%), rash (47%), nail ridging (43%), bruising (33%), and muscle spasms (31%).

The most frequent grade 3 or 4 hematologic adverse events were neutropenia (24%), anemia (14%), and thrombocytopenia (10%). The most common nonhematologic grade 3 adverse event was pneumonia, which occurred in 3 patients (6%).

Nine patients (18%) discontinued treatment. The reasons for discontinuation included disease progression in 5 patients (10%) and death for 3 patients (6%).

This research was sponsored by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute; Danish Cancer Society; Novo Nordisk Foundation; National Institutes of Health Medical Research Scholars Program; and Pharmacyclics Inc.

Ibrutinib is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.