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FDA expands approval of brentuximab vedotin to PTCL
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
When to choose stem cell transplant in PTCL
DUBROVNIK, CROATIA – , according to one expert.
The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.
However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
ATLL
ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).
ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).
Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
Dr. Bazarbachi did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – , according to one expert.
The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.
However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
ATLL
ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).
ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).
Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
Dr. Bazarbachi did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – , according to one expert.
The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.
However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
ATLL
ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).
ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).
Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
Dr. Bazarbachi did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
EXPERT ANALYSIS FROM LEUKEMIA AND LYMPHOMA 2018
AITL responds to 5-azacytidine in small series
Older patients with refractory angioimmunoblastic T cell lymphoma (AITL) appear to respond well to treatment with 5-azacytidine, regardless of mutations.
Francois Lemonnier, MD, of Henri Mondor University Hospitals in Créteil, France, and his colleagues, reported on a retrospective series of 12 AITL patients who received 5-azacytidine for concomitant myeloid neoplasm or as compassionate therapy for relapsed or refractory AITL. The findings were published in Blood.
Patients were given 5-azacytidine subcutaneously at a dose of 75 mg/m2 daily for 7 consecutive days. The treatment was given every 28 days until progression or unacceptable toxicity for a median of 5.5 cycles. Along with 5-azacytidine, half of the patients received rituximab due to the presence of EBV replication or EBV B-blasts in the lymph node biopsy.
The patients were assessed via CT scan and responses were evaluated by investigators following the Cheson criteria.
This was a heavily pretreated patient population. The median age was 70 years and 11 of the patients had relapsed or refractory disease and had received a median of two lines of therapy. There was only one treatment-naive patient in the series.
Treatment with 5-azacytidine produced an overall response rate of 75%, with six patients achieving a complete response and three patients achieving a partial response. The median progression-free survival was 15 months and median overall survival was 21 months at a median follow-up of 27 months.
The researchers noted that some elderly patients with poor performance status achieved a sustained response after treatment with an acceptable tolerance.
Treatment was well tolerated overall. There were no treatment-related deaths and no patients developed neutropenia. Three patients required transfusion and another had grade 3 diarrhea.
The researchers also performed molecular studies using targeted deep sequencing. They detected TET2 mutations in all 12 patients, with seven patients having two mutations. Four patients had DNMT3A mutations, five patients had RHOA mutations, and four patients had p.G17V substitution. One patient had an IDH2R172 mutation.
Since all patients had a TET2 mutation, the researchers were unable to assess its impact on treatment response. However, they saw no association between the number of TET2 mutations and treatment response, or mutations in DNMT3A, IDH2, and RHOA and treatment response.
The study was funded by a grant from the Leukemia & Lymphoma Society. Three of the coauthors received honoraria from Celgene.
SOURCE: Lemonnier F et al. Blood. 2018 Oct 2. doi: 10.1182/blood-2018-04-840538.
Older patients with refractory angioimmunoblastic T cell lymphoma (AITL) appear to respond well to treatment with 5-azacytidine, regardless of mutations.
Francois Lemonnier, MD, of Henri Mondor University Hospitals in Créteil, France, and his colleagues, reported on a retrospective series of 12 AITL patients who received 5-azacytidine for concomitant myeloid neoplasm or as compassionate therapy for relapsed or refractory AITL. The findings were published in Blood.
Patients were given 5-azacytidine subcutaneously at a dose of 75 mg/m2 daily for 7 consecutive days. The treatment was given every 28 days until progression or unacceptable toxicity for a median of 5.5 cycles. Along with 5-azacytidine, half of the patients received rituximab due to the presence of EBV replication or EBV B-blasts in the lymph node biopsy.
The patients were assessed via CT scan and responses were evaluated by investigators following the Cheson criteria.
This was a heavily pretreated patient population. The median age was 70 years and 11 of the patients had relapsed or refractory disease and had received a median of two lines of therapy. There was only one treatment-naive patient in the series.
Treatment with 5-azacytidine produced an overall response rate of 75%, with six patients achieving a complete response and three patients achieving a partial response. The median progression-free survival was 15 months and median overall survival was 21 months at a median follow-up of 27 months.
The researchers noted that some elderly patients with poor performance status achieved a sustained response after treatment with an acceptable tolerance.
Treatment was well tolerated overall. There were no treatment-related deaths and no patients developed neutropenia. Three patients required transfusion and another had grade 3 diarrhea.
The researchers also performed molecular studies using targeted deep sequencing. They detected TET2 mutations in all 12 patients, with seven patients having two mutations. Four patients had DNMT3A mutations, five patients had RHOA mutations, and four patients had p.G17V substitution. One patient had an IDH2R172 mutation.
Since all patients had a TET2 mutation, the researchers were unable to assess its impact on treatment response. However, they saw no association between the number of TET2 mutations and treatment response, or mutations in DNMT3A, IDH2, and RHOA and treatment response.
The study was funded by a grant from the Leukemia & Lymphoma Society. Three of the coauthors received honoraria from Celgene.
SOURCE: Lemonnier F et al. Blood. 2018 Oct 2. doi: 10.1182/blood-2018-04-840538.
Older patients with refractory angioimmunoblastic T cell lymphoma (AITL) appear to respond well to treatment with 5-azacytidine, regardless of mutations.
Francois Lemonnier, MD, of Henri Mondor University Hospitals in Créteil, France, and his colleagues, reported on a retrospective series of 12 AITL patients who received 5-azacytidine for concomitant myeloid neoplasm or as compassionate therapy for relapsed or refractory AITL. The findings were published in Blood.
Patients were given 5-azacytidine subcutaneously at a dose of 75 mg/m2 daily for 7 consecutive days. The treatment was given every 28 days until progression or unacceptable toxicity for a median of 5.5 cycles. Along with 5-azacytidine, half of the patients received rituximab due to the presence of EBV replication or EBV B-blasts in the lymph node biopsy.
The patients were assessed via CT scan and responses were evaluated by investigators following the Cheson criteria.
This was a heavily pretreated patient population. The median age was 70 years and 11 of the patients had relapsed or refractory disease and had received a median of two lines of therapy. There was only one treatment-naive patient in the series.
Treatment with 5-azacytidine produced an overall response rate of 75%, with six patients achieving a complete response and three patients achieving a partial response. The median progression-free survival was 15 months and median overall survival was 21 months at a median follow-up of 27 months.
The researchers noted that some elderly patients with poor performance status achieved a sustained response after treatment with an acceptable tolerance.
Treatment was well tolerated overall. There were no treatment-related deaths and no patients developed neutropenia. Three patients required transfusion and another had grade 3 diarrhea.
The researchers also performed molecular studies using targeted deep sequencing. They detected TET2 mutations in all 12 patients, with seven patients having two mutations. Four patients had DNMT3A mutations, five patients had RHOA mutations, and four patients had p.G17V substitution. One patient had an IDH2R172 mutation.
Since all patients had a TET2 mutation, the researchers were unable to assess its impact on treatment response. However, they saw no association between the number of TET2 mutations and treatment response, or mutations in DNMT3A, IDH2, and RHOA and treatment response.
The study was funded by a grant from the Leukemia & Lymphoma Society. Three of the coauthors received honoraria from Celgene.
SOURCE: Lemonnier F et al. Blood. 2018 Oct 2. doi: 10.1182/blood-2018-04-840538.
FROM BLOOD
Key clinical point:
Major finding: The overall response rate was 75% among the 12 patients, with 6 patients achieving complete response.
Study details: A retrospective case series of 12 patients with angioimmunoblastic T cell lymphoma.
Disclosures: The study was funded by a grant from the Leukemia & Lymphoma Society. Three of the coauthors received honoraria from Celgene.
Source: Lemonnier F et al. Blood. 2018 Oct 2. doi: 10.1182/blood-2018-04-840538.
Brentuximab vendotin plus CHP meets PFS endpoint in ECHELON-2
Takeda Pharmaceuticals and Seattle Genetics announced top-line results in the ECHELON-2 phase 3 trial of brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) in the frontline treatment of CD-30 expressing peripheral T-cell lymphoma (PTCL).
The combination achieved statistically significant improvement in progression-free survival (PFS), compared with the control arm of standard chemotherapy alone using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The PFS was assessed by an Independent Review Facility (hazard ratio, 0.71; P = .0110).
The combination of brentuximab vedotin plus CHP also outperformed CHOP in overall survival, a secondary endpoint of the trial (hazard ratio, 0.66, P = .0244), according to the drug sponsors.
Full results of ECHELON-2 will be presented in December 2018 at the annual meeting of the American Society of Hematology, according to the announcement from Seattle Genetics and Takeda.
Takeda Pharmaceuticals and Seattle Genetics announced top-line results in the ECHELON-2 phase 3 trial of brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) in the frontline treatment of CD-30 expressing peripheral T-cell lymphoma (PTCL).
The combination achieved statistically significant improvement in progression-free survival (PFS), compared with the control arm of standard chemotherapy alone using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The PFS was assessed by an Independent Review Facility (hazard ratio, 0.71; P = .0110).
The combination of brentuximab vedotin plus CHP also outperformed CHOP in overall survival, a secondary endpoint of the trial (hazard ratio, 0.66, P = .0244), according to the drug sponsors.
Full results of ECHELON-2 will be presented in December 2018 at the annual meeting of the American Society of Hematology, according to the announcement from Seattle Genetics and Takeda.
Takeda Pharmaceuticals and Seattle Genetics announced top-line results in the ECHELON-2 phase 3 trial of brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) in the frontline treatment of CD-30 expressing peripheral T-cell lymphoma (PTCL).
The combination achieved statistically significant improvement in progression-free survival (PFS), compared with the control arm of standard chemotherapy alone using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The PFS was assessed by an Independent Review Facility (hazard ratio, 0.71; P = .0110).
The combination of brentuximab vedotin plus CHP also outperformed CHOP in overall survival, a secondary endpoint of the trial (hazard ratio, 0.66, P = .0244), according to the drug sponsors.
Full results of ECHELON-2 will be presented in December 2018 at the annual meeting of the American Society of Hematology, according to the announcement from Seattle Genetics and Takeda.
FDA lifts partial hold on tazemetostat trials
The U.S. Food and Drug Administration has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas, according to a press release from the drug’s developer Epizyme.
The patient had been on study for approximately 15 months and had achieved a confirmed partial response. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” Robert Bazemore, president and chief executive officer of Epizyme, said in a webcast on Sept. 24.
Epizyme assessed the risk of secondary malignancies, including T-LBL, as well as the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials. A panel of external scientific and medical experts who reviewed the findings concluded that T-LBL risks appear to be confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
“The team at Epizyme has worked diligently in collaboration with external experts and the FDA over the past several months,” Mr. Bazemore said.
The company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials. However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies. Mr. Bazemore said Epizyme hopes to submit a New Drug Application for tazemetostat in the treatment of epithelioid sarcoma.
Tazemetostat is under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid-tumor malignancies. The drug is also being studied as part of combination therapy for non–small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Epizyme is now working to resolve partial clinical holds placed on tazemetostat in France and Germany in order to resume trial enrollment in those countries.
The U.S. Food and Drug Administration has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas, according to a press release from the drug’s developer Epizyme.
The patient had been on study for approximately 15 months and had achieved a confirmed partial response. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” Robert Bazemore, president and chief executive officer of Epizyme, said in a webcast on Sept. 24.
Epizyme assessed the risk of secondary malignancies, including T-LBL, as well as the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials. A panel of external scientific and medical experts who reviewed the findings concluded that T-LBL risks appear to be confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
“The team at Epizyme has worked diligently in collaboration with external experts and the FDA over the past several months,” Mr. Bazemore said.
The company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials. However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies. Mr. Bazemore said Epizyme hopes to submit a New Drug Application for tazemetostat in the treatment of epithelioid sarcoma.
Tazemetostat is under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid-tumor malignancies. The drug is also being studied as part of combination therapy for non–small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Epizyme is now working to resolve partial clinical holds placed on tazemetostat in France and Germany in order to resume trial enrollment in those countries.
The U.S. Food and Drug Administration has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas, according to a press release from the drug’s developer Epizyme.
The patient had been on study for approximately 15 months and had achieved a confirmed partial response. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” Robert Bazemore, president and chief executive officer of Epizyme, said in a webcast on Sept. 24.
Epizyme assessed the risk of secondary malignancies, including T-LBL, as well as the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials. A panel of external scientific and medical experts who reviewed the findings concluded that T-LBL risks appear to be confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
“The team at Epizyme has worked diligently in collaboration with external experts and the FDA over the past several months,” Mr. Bazemore said.
The company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials. However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies. Mr. Bazemore said Epizyme hopes to submit a New Drug Application for tazemetostat in the treatment of epithelioid sarcoma.
Tazemetostat is under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid-tumor malignancies. The drug is also being studied as part of combination therapy for non–small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Epizyme is now working to resolve partial clinical holds placed on tazemetostat in France and Germany in order to resume trial enrollment in those countries.
Researchers find drug target in anaplastic large-cell lymphoma
Preclinical research indicates that TYK2 inhibitors could be effective in treating anaplastic large-cell lymphoma (ALCL).
Researchers found evidence to suggest that TYK2 “is highly expressed in all cases of human ALCL.”
The team also discovered that TYK2 inhibition induces apoptosis in human ALCL cells, and it delays tumor onset, and prolongs survival in a mouse model of ALCL.
Olaf Merkel, PhD, of the Medical University of Vienna in Austria, and his colleagues detailed these findings in Leukemia.
The researchers said their analyses suggest TYK2 is expressed in all types of ALCL, regardless of ALK status, and TYK2 mediates the same anti-apoptotic response across ALCLs.
“Therefore, we could consider TYK2 signaling as the Achilles’ heel of ALCL, as, in all patients we have analyzed, the tumor cells relied on this activity to support the essential survival signal,” Dr. Merkel said in a statement.
He and his colleagues found that disrupting TYK2 – either via gene knockdown or with small-molecule TYK2 inhibitors – induced apoptosis in human ALCL cells in vitro.
In a mouse model of NPM-ALK-induced lymphoma, Tyk2 deletion slowed the rate of tumor growth and significantly prolonged survival. The median survival was 53.3 weeks in mice with Tyk2 deletion and 16.0 weeks in control mice (P less than .0001).
Additional experiments in human ALCL cell lines showed that “TYK2 is activated by autocrine production of IL-10 and IL-22 and by interaction with specific receptors expressed by the cells,” the researchers said.
They also found that “activated TYK2 leads to STAT1 and STAT3 phosphorylation, activated expression of MCL1, and aberrant ALCL cell survival.”
Taking these findings together, the researchers concluded that TYK2 inhibitors could be effective for treating ALCL.
“We are looking forward to TYK2 inhibitors becoming available,” said study coauthor Lukas Kenner, MD, of the Medical University of Vienna. “[I]n the more rare lymphomas, we urgently need better therapies.”
The researchers received grant funding from various organizations but reported having no conflicts of interest.
SOURCE: Prutsch N et al. Leukemia. 2018 Aug 21. doi: 10.1038/s41375-018-0239-1.
Preclinical research indicates that TYK2 inhibitors could be effective in treating anaplastic large-cell lymphoma (ALCL).
Researchers found evidence to suggest that TYK2 “is highly expressed in all cases of human ALCL.”
The team also discovered that TYK2 inhibition induces apoptosis in human ALCL cells, and it delays tumor onset, and prolongs survival in a mouse model of ALCL.
Olaf Merkel, PhD, of the Medical University of Vienna in Austria, and his colleagues detailed these findings in Leukemia.
The researchers said their analyses suggest TYK2 is expressed in all types of ALCL, regardless of ALK status, and TYK2 mediates the same anti-apoptotic response across ALCLs.
“Therefore, we could consider TYK2 signaling as the Achilles’ heel of ALCL, as, in all patients we have analyzed, the tumor cells relied on this activity to support the essential survival signal,” Dr. Merkel said in a statement.
He and his colleagues found that disrupting TYK2 – either via gene knockdown or with small-molecule TYK2 inhibitors – induced apoptosis in human ALCL cells in vitro.
In a mouse model of NPM-ALK-induced lymphoma, Tyk2 deletion slowed the rate of tumor growth and significantly prolonged survival. The median survival was 53.3 weeks in mice with Tyk2 deletion and 16.0 weeks in control mice (P less than .0001).
Additional experiments in human ALCL cell lines showed that “TYK2 is activated by autocrine production of IL-10 and IL-22 and by interaction with specific receptors expressed by the cells,” the researchers said.
They also found that “activated TYK2 leads to STAT1 and STAT3 phosphorylation, activated expression of MCL1, and aberrant ALCL cell survival.”
Taking these findings together, the researchers concluded that TYK2 inhibitors could be effective for treating ALCL.
“We are looking forward to TYK2 inhibitors becoming available,” said study coauthor Lukas Kenner, MD, of the Medical University of Vienna. “[I]n the more rare lymphomas, we urgently need better therapies.”
The researchers received grant funding from various organizations but reported having no conflicts of interest.
SOURCE: Prutsch N et al. Leukemia. 2018 Aug 21. doi: 10.1038/s41375-018-0239-1.
Preclinical research indicates that TYK2 inhibitors could be effective in treating anaplastic large-cell lymphoma (ALCL).
Researchers found evidence to suggest that TYK2 “is highly expressed in all cases of human ALCL.”
The team also discovered that TYK2 inhibition induces apoptosis in human ALCL cells, and it delays tumor onset, and prolongs survival in a mouse model of ALCL.
Olaf Merkel, PhD, of the Medical University of Vienna in Austria, and his colleagues detailed these findings in Leukemia.
The researchers said their analyses suggest TYK2 is expressed in all types of ALCL, regardless of ALK status, and TYK2 mediates the same anti-apoptotic response across ALCLs.
“Therefore, we could consider TYK2 signaling as the Achilles’ heel of ALCL, as, in all patients we have analyzed, the tumor cells relied on this activity to support the essential survival signal,” Dr. Merkel said in a statement.
He and his colleagues found that disrupting TYK2 – either via gene knockdown or with small-molecule TYK2 inhibitors – induced apoptosis in human ALCL cells in vitro.
In a mouse model of NPM-ALK-induced lymphoma, Tyk2 deletion slowed the rate of tumor growth and significantly prolonged survival. The median survival was 53.3 weeks in mice with Tyk2 deletion and 16.0 weeks in control mice (P less than .0001).
Additional experiments in human ALCL cell lines showed that “TYK2 is activated by autocrine production of IL-10 and IL-22 and by interaction with specific receptors expressed by the cells,” the researchers said.
They also found that “activated TYK2 leads to STAT1 and STAT3 phosphorylation, activated expression of MCL1, and aberrant ALCL cell survival.”
Taking these findings together, the researchers concluded that TYK2 inhibitors could be effective for treating ALCL.
“We are looking forward to TYK2 inhibitors becoming available,” said study coauthor Lukas Kenner, MD, of the Medical University of Vienna. “[I]n the more rare lymphomas, we urgently need better therapies.”
The researchers received grant funding from various organizations but reported having no conflicts of interest.
SOURCE: Prutsch N et al. Leukemia. 2018 Aug 21. doi: 10.1038/s41375-018-0239-1.
FROM LEUKEMIA
Key clinical point:
Major finding: TYK2 was expressed in all types of ALCL studied and mediated the same anti-apoptotic response across ALCLs.
Study details: A preclinical study of mouse and human ALCL cell lines.
Disclosures: The researchers received grant funding from various organizations but reported having no conflicts of interest.
Source: Prutsch N et al. Leukemia. 2018 Aug 21. doi: 10.1038/s41375-018-0239-1.
CPI-613 receives orphan designation for PTCL
The Food and Drug Administration has granted orphan drug designation to CPI-613 for the treatment of peripheral T-cell lymphoma (PTCL).
CPI-613 is a novel lipoic acid analogue that inhibits multiple enzyme targets within the tricarboxylic acid cycle.
Rafael Pharmaceuticals is developing CPI-613 as a treatment for hematologic malignancies and solid tumors.
CPI-613 is currently under investigation in combination with bendamustine in a phase 1 study of patients with relapsed or refractory T-cell lymphoma or classical Hodgkin lymphoma, according to the press release from the company.
Results from this trial were presented at the 2016 annual meeting of the American Society of Hematology.
CPI-613 was given at escalating doses starting at 2,000 mg/m2 over 2 hours on days 1-4 as well as on days 8, 11, 15, and 18. Bendamustine was infused at 90 mg/m2 on days 4 and 5 of each 4-week treatment cycle. The treatment cycles were repeated for up to six cycles. There was no intrapatient dose escalation.
The ASH presentation included safety data on eight patients. The most common grade 3 or higher toxicities – lymphopenia and neutropenia – occurred in four patients.
A patient dosed at 2,750 mg/m2 had a dose-limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. Because of this, the study protocol was amended to discontinue dose escalation at doses of 2,750 mg/m2 or higher and to expand the 2,500 mg/m2 cohort.
Six patients were evaluable for efficacy, and the overall response rate was 83% (5/6).
There were three complete responses in patients with PTCL not otherwise specified, a partial response in a patient with mycosis fungoides, and a partial response in a patient with angioimmunoblastic T-cell lymphoma.
One patient with T-cell acute lymphoblastic leukemia experienced progressive disease.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The Food and Drug Administration has granted orphan drug designation to CPI-613 for the treatment of peripheral T-cell lymphoma (PTCL).
CPI-613 is a novel lipoic acid analogue that inhibits multiple enzyme targets within the tricarboxylic acid cycle.
Rafael Pharmaceuticals is developing CPI-613 as a treatment for hematologic malignancies and solid tumors.
CPI-613 is currently under investigation in combination with bendamustine in a phase 1 study of patients with relapsed or refractory T-cell lymphoma or classical Hodgkin lymphoma, according to the press release from the company.
Results from this trial were presented at the 2016 annual meeting of the American Society of Hematology.
CPI-613 was given at escalating doses starting at 2,000 mg/m2 over 2 hours on days 1-4 as well as on days 8, 11, 15, and 18. Bendamustine was infused at 90 mg/m2 on days 4 and 5 of each 4-week treatment cycle. The treatment cycles were repeated for up to six cycles. There was no intrapatient dose escalation.
The ASH presentation included safety data on eight patients. The most common grade 3 or higher toxicities – lymphopenia and neutropenia – occurred in four patients.
A patient dosed at 2,750 mg/m2 had a dose-limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. Because of this, the study protocol was amended to discontinue dose escalation at doses of 2,750 mg/m2 or higher and to expand the 2,500 mg/m2 cohort.
Six patients were evaluable for efficacy, and the overall response rate was 83% (5/6).
There were three complete responses in patients with PTCL not otherwise specified, a partial response in a patient with mycosis fungoides, and a partial response in a patient with angioimmunoblastic T-cell lymphoma.
One patient with T-cell acute lymphoblastic leukemia experienced progressive disease.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The Food and Drug Administration has granted orphan drug designation to CPI-613 for the treatment of peripheral T-cell lymphoma (PTCL).
CPI-613 is a novel lipoic acid analogue that inhibits multiple enzyme targets within the tricarboxylic acid cycle.
Rafael Pharmaceuticals is developing CPI-613 as a treatment for hematologic malignancies and solid tumors.
CPI-613 is currently under investigation in combination with bendamustine in a phase 1 study of patients with relapsed or refractory T-cell lymphoma or classical Hodgkin lymphoma, according to the press release from the company.
Results from this trial were presented at the 2016 annual meeting of the American Society of Hematology.
CPI-613 was given at escalating doses starting at 2,000 mg/m2 over 2 hours on days 1-4 as well as on days 8, 11, 15, and 18. Bendamustine was infused at 90 mg/m2 on days 4 and 5 of each 4-week treatment cycle. The treatment cycles were repeated for up to six cycles. There was no intrapatient dose escalation.
The ASH presentation included safety data on eight patients. The most common grade 3 or higher toxicities – lymphopenia and neutropenia – occurred in four patients.
A patient dosed at 2,750 mg/m2 had a dose-limiting toxicity of grade 3 acute kidney injury and grade 4 lactic acidosis. Because of this, the study protocol was amended to discontinue dose escalation at doses of 2,750 mg/m2 or higher and to expand the 2,500 mg/m2 cohort.
Six patients were evaluable for efficacy, and the overall response rate was 83% (5/6).
There were three complete responses in patients with PTCL not otherwise specified, a partial response in a patient with mycosis fungoides, and a partial response in a patient with angioimmunoblastic T-cell lymphoma.
One patient with T-cell acute lymphoblastic leukemia experienced progressive disease.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Make The Diagnosis - September 2018
Some have postulated an infectious agent as the cause. Atopic dermatitis may confer an increased risk because of the chronic stimulation of T cells. Males are more commonly affected than females by a 2:1 ratio. A worse prognosis is associated with advanced age. Children and adolescents may be affected as well.
With mycosis fungoides, there are three main types of skin lesions: patch, plaque, and tumor. Patients will progress from patch to plaque to tumor stage in classic MF. Often, lesions begin as scaly, erythematous patches that resemble eczema. Because of the nonspecific nature of early lesions, the median duration from the onset of skin lesions to the diagnosis of MF is 4-6 years. Patch stage lesions may be pruritic or asymptomatic. Commonly, they present in non–sun-exposed areas, such as the buttocks. Annular, infiltrated, red-brown or violaceous plaques can develop, which represent malignant T-cell infiltration. Many patients never progress past the plaque stage. Tumor stage MF is more aggressive, with nodules that may undergo necrosis and ulceration.
The leukemic form of MF is Sézary syndrome. Patients present with pruritic erythroderma and lymphadenopathy. Nail dystrophy, scaling of palms and soles, and alopecia may be present. A peripheral blood smear reveals Sézary cells, which are large, hyperconvoluted lymphocytes. The count of Sézary cells is usually greater than 1000 cells/mm3.
Histology of early lesions may not be diagnostic for CTCL. Often, biopsies will be read as eczematous or psoriasiform for years before the diagnosis of MF is made. Classically, epidermotropism (single-cell exocytosis of lymphocytes into the epidermis) is present. Advanced stages may show a dense infiltrate of lymphocytes in the dermis. Groups of lymphocytes in the epidermis form Pautrier’s microabscesses. Mycosis cells may exhibit cerebriform nuclei. Neoplastic cells in MF are CD3+, CD4+, CD45RO+, CD8–. Tissue can be sent for T-cell gene rearrangement polymerase chain reaction. The presence of monoclonal T-cell gene receptor rearrangements can aid in the diagnosis of MF.
Treatment includes topical steroids, mechlorethamine (nitrogen mustard) or bexarotene gel, PUVA therapy, and narrow-band UVB light for limited and/or patch disease. Localized radiotherapy can be used for more resistant lesions. Topical therapies are preferred in the early stages in MF. Systemic treatments for patients who do not respond to local therapy, or in more advanced disease include methotrexate, interferon-alpha, oral bexarotene, denileukin diftitox, and combination chemotherapy. Photopheresis is reserved for erythrodermic disease.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
Some have postulated an infectious agent as the cause. Atopic dermatitis may confer an increased risk because of the chronic stimulation of T cells. Males are more commonly affected than females by a 2:1 ratio. A worse prognosis is associated with advanced age. Children and adolescents may be affected as well.
With mycosis fungoides, there are three main types of skin lesions: patch, plaque, and tumor. Patients will progress from patch to plaque to tumor stage in classic MF. Often, lesions begin as scaly, erythematous patches that resemble eczema. Because of the nonspecific nature of early lesions, the median duration from the onset of skin lesions to the diagnosis of MF is 4-6 years. Patch stage lesions may be pruritic or asymptomatic. Commonly, they present in non–sun-exposed areas, such as the buttocks. Annular, infiltrated, red-brown or violaceous plaques can develop, which represent malignant T-cell infiltration. Many patients never progress past the plaque stage. Tumor stage MF is more aggressive, with nodules that may undergo necrosis and ulceration.
The leukemic form of MF is Sézary syndrome. Patients present with pruritic erythroderma and lymphadenopathy. Nail dystrophy, scaling of palms and soles, and alopecia may be present. A peripheral blood smear reveals Sézary cells, which are large, hyperconvoluted lymphocytes. The count of Sézary cells is usually greater than 1000 cells/mm3.
Histology of early lesions may not be diagnostic for CTCL. Often, biopsies will be read as eczematous or psoriasiform for years before the diagnosis of MF is made. Classically, epidermotropism (single-cell exocytosis of lymphocytes into the epidermis) is present. Advanced stages may show a dense infiltrate of lymphocytes in the dermis. Groups of lymphocytes in the epidermis form Pautrier’s microabscesses. Mycosis cells may exhibit cerebriform nuclei. Neoplastic cells in MF are CD3+, CD4+, CD45RO+, CD8–. Tissue can be sent for T-cell gene rearrangement polymerase chain reaction. The presence of monoclonal T-cell gene receptor rearrangements can aid in the diagnosis of MF.
Treatment includes topical steroids, mechlorethamine (nitrogen mustard) or bexarotene gel, PUVA therapy, and narrow-band UVB light for limited and/or patch disease. Localized radiotherapy can be used for more resistant lesions. Topical therapies are preferred in the early stages in MF. Systemic treatments for patients who do not respond to local therapy, or in more advanced disease include methotrexate, interferon-alpha, oral bexarotene, denileukin diftitox, and combination chemotherapy. Photopheresis is reserved for erythrodermic disease.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
Some have postulated an infectious agent as the cause. Atopic dermatitis may confer an increased risk because of the chronic stimulation of T cells. Males are more commonly affected than females by a 2:1 ratio. A worse prognosis is associated with advanced age. Children and adolescents may be affected as well.
With mycosis fungoides, there are three main types of skin lesions: patch, plaque, and tumor. Patients will progress from patch to plaque to tumor stage in classic MF. Often, lesions begin as scaly, erythematous patches that resemble eczema. Because of the nonspecific nature of early lesions, the median duration from the onset of skin lesions to the diagnosis of MF is 4-6 years. Patch stage lesions may be pruritic or asymptomatic. Commonly, they present in non–sun-exposed areas, such as the buttocks. Annular, infiltrated, red-brown or violaceous plaques can develop, which represent malignant T-cell infiltration. Many patients never progress past the plaque stage. Tumor stage MF is more aggressive, with nodules that may undergo necrosis and ulceration.
The leukemic form of MF is Sézary syndrome. Patients present with pruritic erythroderma and lymphadenopathy. Nail dystrophy, scaling of palms and soles, and alopecia may be present. A peripheral blood smear reveals Sézary cells, which are large, hyperconvoluted lymphocytes. The count of Sézary cells is usually greater than 1000 cells/mm3.
Histology of early lesions may not be diagnostic for CTCL. Often, biopsies will be read as eczematous or psoriasiform for years before the diagnosis of MF is made. Classically, epidermotropism (single-cell exocytosis of lymphocytes into the epidermis) is present. Advanced stages may show a dense infiltrate of lymphocytes in the dermis. Groups of lymphocytes in the epidermis form Pautrier’s microabscesses. Mycosis cells may exhibit cerebriform nuclei. Neoplastic cells in MF are CD3+, CD4+, CD45RO+, CD8–. Tissue can be sent for T-cell gene rearrangement polymerase chain reaction. The presence of monoclonal T-cell gene receptor rearrangements can aid in the diagnosis of MF.
Treatment includes topical steroids, mechlorethamine (nitrogen mustard) or bexarotene gel, PUVA therapy, and narrow-band UVB light for limited and/or patch disease. Localized radiotherapy can be used for more resistant lesions. Topical therapies are preferred in the early stages in MF. Systemic treatments for patients who do not respond to local therapy, or in more advanced disease include methotrexate, interferon-alpha, oral bexarotene, denileukin diftitox, and combination chemotherapy. Photopheresis is reserved for erythrodermic disease.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
New regimens for youth with T-cell malignancies yield best outcomes yet
A set of novel chemotherapy regimens yield excellent outcomes—the best yet—among pediatric and young adult patients with T-cell malignancies, finds a phase 3 randomized controlled trial conducted by the Children’s Oncology Group (ALL0434).
“Despite very intense and complex chemotherapy, 20% of children and adolescents enrolled in Children’s Oncology Group T-cell leukemia trials between 2000 and 2005 did not survive. New drugs were needed to improve survival rates for T-cell malignancies,” lead study author Kimberly P. Dunsmore, MD, a professor at Virginia Tech, Roanoke, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.
The ALL0434 trial tested the addition of methotrexate (Trexall) and/or nelarabine (Arranon), a T cell–specific drug known to be efficacious in relapsed disease, to standard chemotherapy, with tailoring of the regimen to recurrence risk. Analyses were based on 1,545 patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL).
Results for all patients with T-ALL showed that, with addition of either or both drugs, more than 90% were alive at 4 years and more than 80% were leukemia free. Adding nelarabine to standard chemotherapy improved disease-free survival among the subset having intermediate- or high-risk disease, and the best outcomes were seen with addition of both nelarabine and an escalating dose of methotrexate.
Although patients with T-LL did not see benefit from addition of nelarabine, they still had an 85% rate of overall survival at 4 years.
“ALL0434 is the largest trial for children and young adults with T-cell malignancy ever conducted. It has the best-ever survival data,” Dr. Dunsmore commented.
“Our next steps will be to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation. This is to decrease long-term neurologic side effects, and we think it may be possible since nelarabine also reduces CNS relapses,” she said.
“This trial highlights how effective our pediatric and young adult oncologists are at accruing: This is a rare disease, and they were able to put more than 1,500 patients on trial with this rare disease over the course of time,” commented ASCO President Bruce E. Johnson, MD, FASCO.
The new combination regimens are noteworthy in that they improved survival by an absolute 10% without minimal increase in toxicity, he maintained.
“This is part of the paradigm where nelarabine had been approved [by the FDA] for relapsed or recurrent disease, and in this particular setting, it has been moved upfront, closer to the initial treatment, improving the outcomes for those patients,” elaborated Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, both in Boston.
Study details
The ALL0434 trial enrolled patients aged 1-30 years with newly diagnosed T-ALL or T-LL. After induction chemotherapy, all patients received standard chemotherapy, the Children’s Oncology Group augmented Berlin-Frankfurt-Munster regimen (N Engl J Med. 1998;338:1663-71), and depending on recurrence risk, cranial irradiation.
In addition to that regimen, they were randomly assigned to four arms, according to methotrexate dosing (high dose with leucovorin rescue in the inpatient setting vs. escalating dose in the outpatient setting) and nelarabine therapy (receipt vs. nonreceipt).
Among patients with T-ALL, those with low-risk disease were ineligible for nelarabine and did not receive cranial irradiation, whereas those with intermediate- and high-risk disease were randomized to all four arms, Dr. Dunsmore explained. In addition, those who did not achieve remission on induction chemotherapy were nonrandomly assigned to the high-dose methotrexate plus nelarabine arm.
Patients with T-LL were ineligible for high-dose methotrexate and were randomized to escalating-dose methotrexate with or without nelarabine.
Among all patients with T-ALL, the 4-year rate of overall survival was 90.2%, and the 4-year rate of disease-free survival was 84.1%, Dr. Dunsmore reported.
Disease-free survival was better with escalating-dose methotrexate than with high-dose methotrexate (89.8% vs. 78%).
Addition of nelarabine for patients with T-ALL having intermediate- or high-risk disease improved disease-free survival, from 83% without the drug to 88% with the drug (P = .0450), and reduced the rate of CNS relapse. Disease-free survival was highest, at 91%, among those who received both escalating-dose methotrexate and nelarabine.
Among the patients who did not achieve remission from induction chemotherapy, the 4-year rate of overall survival was 54%. “This is important because it’s more than double the past survival rates,” Dr. Dunsmore noted.
Patients with T-LL fared similarly well whether they received nelarabine or not; fully 85% overall were still alive at 4 years.
In terms of adverse effects of nelarabine therapy, the rate of peripheral neuropathy (motor or sensory), one of the more problematic adverse effects of the drug, was 8% in the trial population overall and did not exceed 9% in any treatment arm, she reported.
Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero Technologies; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.
SOURCE: Dunsmore KP et al. ASCO 2018, Abstract 10500.
A set of novel chemotherapy regimens yield excellent outcomes—the best yet—among pediatric and young adult patients with T-cell malignancies, finds a phase 3 randomized controlled trial conducted by the Children’s Oncology Group (ALL0434).
“Despite very intense and complex chemotherapy, 20% of children and adolescents enrolled in Children’s Oncology Group T-cell leukemia trials between 2000 and 2005 did not survive. New drugs were needed to improve survival rates for T-cell malignancies,” lead study author Kimberly P. Dunsmore, MD, a professor at Virginia Tech, Roanoke, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.
The ALL0434 trial tested the addition of methotrexate (Trexall) and/or nelarabine (Arranon), a T cell–specific drug known to be efficacious in relapsed disease, to standard chemotherapy, with tailoring of the regimen to recurrence risk. Analyses were based on 1,545 patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL).
Results for all patients with T-ALL showed that, with addition of either or both drugs, more than 90% were alive at 4 years and more than 80% were leukemia free. Adding nelarabine to standard chemotherapy improved disease-free survival among the subset having intermediate- or high-risk disease, and the best outcomes were seen with addition of both nelarabine and an escalating dose of methotrexate.
Although patients with T-LL did not see benefit from addition of nelarabine, they still had an 85% rate of overall survival at 4 years.
“ALL0434 is the largest trial for children and young adults with T-cell malignancy ever conducted. It has the best-ever survival data,” Dr. Dunsmore commented.
“Our next steps will be to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation. This is to decrease long-term neurologic side effects, and we think it may be possible since nelarabine also reduces CNS relapses,” she said.
“This trial highlights how effective our pediatric and young adult oncologists are at accruing: This is a rare disease, and they were able to put more than 1,500 patients on trial with this rare disease over the course of time,” commented ASCO President Bruce E. Johnson, MD, FASCO.
The new combination regimens are noteworthy in that they improved survival by an absolute 10% without minimal increase in toxicity, he maintained.
“This is part of the paradigm where nelarabine had been approved [by the FDA] for relapsed or recurrent disease, and in this particular setting, it has been moved upfront, closer to the initial treatment, improving the outcomes for those patients,” elaborated Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, both in Boston.
Study details
The ALL0434 trial enrolled patients aged 1-30 years with newly diagnosed T-ALL or T-LL. After induction chemotherapy, all patients received standard chemotherapy, the Children’s Oncology Group augmented Berlin-Frankfurt-Munster regimen (N Engl J Med. 1998;338:1663-71), and depending on recurrence risk, cranial irradiation.
In addition to that regimen, they were randomly assigned to four arms, according to methotrexate dosing (high dose with leucovorin rescue in the inpatient setting vs. escalating dose in the outpatient setting) and nelarabine therapy (receipt vs. nonreceipt).
Among patients with T-ALL, those with low-risk disease were ineligible for nelarabine and did not receive cranial irradiation, whereas those with intermediate- and high-risk disease were randomized to all four arms, Dr. Dunsmore explained. In addition, those who did not achieve remission on induction chemotherapy were nonrandomly assigned to the high-dose methotrexate plus nelarabine arm.
Patients with T-LL were ineligible for high-dose methotrexate and were randomized to escalating-dose methotrexate with or without nelarabine.
Among all patients with T-ALL, the 4-year rate of overall survival was 90.2%, and the 4-year rate of disease-free survival was 84.1%, Dr. Dunsmore reported.
Disease-free survival was better with escalating-dose methotrexate than with high-dose methotrexate (89.8% vs. 78%).
Addition of nelarabine for patients with T-ALL having intermediate- or high-risk disease improved disease-free survival, from 83% without the drug to 88% with the drug (P = .0450), and reduced the rate of CNS relapse. Disease-free survival was highest, at 91%, among those who received both escalating-dose methotrexate and nelarabine.
Among the patients who did not achieve remission from induction chemotherapy, the 4-year rate of overall survival was 54%. “This is important because it’s more than double the past survival rates,” Dr. Dunsmore noted.
Patients with T-LL fared similarly well whether they received nelarabine or not; fully 85% overall were still alive at 4 years.
In terms of adverse effects of nelarabine therapy, the rate of peripheral neuropathy (motor or sensory), one of the more problematic adverse effects of the drug, was 8% in the trial population overall and did not exceed 9% in any treatment arm, she reported.
Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero Technologies; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.
SOURCE: Dunsmore KP et al. ASCO 2018, Abstract 10500.
A set of novel chemotherapy regimens yield excellent outcomes—the best yet—among pediatric and young adult patients with T-cell malignancies, finds a phase 3 randomized controlled trial conducted by the Children’s Oncology Group (ALL0434).
“Despite very intense and complex chemotherapy, 20% of children and adolescents enrolled in Children’s Oncology Group T-cell leukemia trials between 2000 and 2005 did not survive. New drugs were needed to improve survival rates for T-cell malignancies,” lead study author Kimberly P. Dunsmore, MD, a professor at Virginia Tech, Roanoke, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.
The ALL0434 trial tested the addition of methotrexate (Trexall) and/or nelarabine (Arranon), a T cell–specific drug known to be efficacious in relapsed disease, to standard chemotherapy, with tailoring of the regimen to recurrence risk. Analyses were based on 1,545 patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL).
Results for all patients with T-ALL showed that, with addition of either or both drugs, more than 90% were alive at 4 years and more than 80% were leukemia free. Adding nelarabine to standard chemotherapy improved disease-free survival among the subset having intermediate- or high-risk disease, and the best outcomes were seen with addition of both nelarabine and an escalating dose of methotrexate.
Although patients with T-LL did not see benefit from addition of nelarabine, they still had an 85% rate of overall survival at 4 years.
“ALL0434 is the largest trial for children and young adults with T-cell malignancy ever conducted. It has the best-ever survival data,” Dr. Dunsmore commented.
“Our next steps will be to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation. This is to decrease long-term neurologic side effects, and we think it may be possible since nelarabine also reduces CNS relapses,” she said.
“This trial highlights how effective our pediatric and young adult oncologists are at accruing: This is a rare disease, and they were able to put more than 1,500 patients on trial with this rare disease over the course of time,” commented ASCO President Bruce E. Johnson, MD, FASCO.
The new combination regimens are noteworthy in that they improved survival by an absolute 10% without minimal increase in toxicity, he maintained.
“This is part of the paradigm where nelarabine had been approved [by the FDA] for relapsed or recurrent disease, and in this particular setting, it has been moved upfront, closer to the initial treatment, improving the outcomes for those patients,” elaborated Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, both in Boston.
Study details
The ALL0434 trial enrolled patients aged 1-30 years with newly diagnosed T-ALL or T-LL. After induction chemotherapy, all patients received standard chemotherapy, the Children’s Oncology Group augmented Berlin-Frankfurt-Munster regimen (N Engl J Med. 1998;338:1663-71), and depending on recurrence risk, cranial irradiation.
In addition to that regimen, they were randomly assigned to four arms, according to methotrexate dosing (high dose with leucovorin rescue in the inpatient setting vs. escalating dose in the outpatient setting) and nelarabine therapy (receipt vs. nonreceipt).
Among patients with T-ALL, those with low-risk disease were ineligible for nelarabine and did not receive cranial irradiation, whereas those with intermediate- and high-risk disease were randomized to all four arms, Dr. Dunsmore explained. In addition, those who did not achieve remission on induction chemotherapy were nonrandomly assigned to the high-dose methotrexate plus nelarabine arm.
Patients with T-LL were ineligible for high-dose methotrexate and were randomized to escalating-dose methotrexate with or without nelarabine.
Among all patients with T-ALL, the 4-year rate of overall survival was 90.2%, and the 4-year rate of disease-free survival was 84.1%, Dr. Dunsmore reported.
Disease-free survival was better with escalating-dose methotrexate than with high-dose methotrexate (89.8% vs. 78%).
Addition of nelarabine for patients with T-ALL having intermediate- or high-risk disease improved disease-free survival, from 83% without the drug to 88% with the drug (P = .0450), and reduced the rate of CNS relapse. Disease-free survival was highest, at 91%, among those who received both escalating-dose methotrexate and nelarabine.
Among the patients who did not achieve remission from induction chemotherapy, the 4-year rate of overall survival was 54%. “This is important because it’s more than double the past survival rates,” Dr. Dunsmore noted.
Patients with T-LL fared similarly well whether they received nelarabine or not; fully 85% overall were still alive at 4 years.
In terms of adverse effects of nelarabine therapy, the rate of peripheral neuropathy (motor or sensory), one of the more problematic adverse effects of the drug, was 8% in the trial population overall and did not exceed 9% in any treatment arm, she reported.
Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero Technologies; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.
SOURCE: Dunsmore KP et al. ASCO 2018, Abstract 10500.
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: Patients with T-ALL had a 4-year rate of overall survival of 90.2% and disease-free survival of 84.1%; patients with T-LL had a 4-year rate of overall survival of 85%.
Study details: Phase 3 randomized controlled trial among 1,545 youth with T-ALL or T-LL testing various regimens of methotrexate and/or nelarabine with standard chemotherapy (ALL0434).
Disclosures: Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.
Source: Dunsmore KP et al. ASCO 2018, Abstract 10500.
FDA places partial hold on trials after secondary lymphoma
The drugmaker after a pediatric patient developed a secondary T-cell lymphoma.
The Food and Drug Administration had issued a partial clinical hold in April on new enrollment of any patients with genetically defined solid tumors and hematologic malignancies. Patients already enrolled who have not had disease progression can continue to receive tazemetostat.
Tazemetostat is a first-in-class EZH2 inhibitor being studied as monotherapy in phase 1 and 2 trials for certain molecularly defined solid tumors, follicular lymphoma and diffuse large B-cell lymphoma, mesothelioma, and in combination studies of DLBCL and non–small cell lung cancer.
Epizyme is currently working to update informed consent, the investigator’s brochure, and study protocols, the company said in a statement.
The drugmaker after a pediatric patient developed a secondary T-cell lymphoma.
The Food and Drug Administration had issued a partial clinical hold in April on new enrollment of any patients with genetically defined solid tumors and hematologic malignancies. Patients already enrolled who have not had disease progression can continue to receive tazemetostat.
Tazemetostat is a first-in-class EZH2 inhibitor being studied as monotherapy in phase 1 and 2 trials for certain molecularly defined solid tumors, follicular lymphoma and diffuse large B-cell lymphoma, mesothelioma, and in combination studies of DLBCL and non–small cell lung cancer.
Epizyme is currently working to update informed consent, the investigator’s brochure, and study protocols, the company said in a statement.
The drugmaker after a pediatric patient developed a secondary T-cell lymphoma.
The Food and Drug Administration had issued a partial clinical hold in April on new enrollment of any patients with genetically defined solid tumors and hematologic malignancies. Patients already enrolled who have not had disease progression can continue to receive tazemetostat.
Tazemetostat is a first-in-class EZH2 inhibitor being studied as monotherapy in phase 1 and 2 trials for certain molecularly defined solid tumors, follicular lymphoma and diffuse large B-cell lymphoma, mesothelioma, and in combination studies of DLBCL and non–small cell lung cancer.
Epizyme is currently working to update informed consent, the investigator’s brochure, and study protocols, the company said in a statement.