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Jennifer Smith is the editor of Oncology Practice, part of MDedge Hematology/Oncology. She was previously the editor of Hematology Times, an editor at Principal Investigators Association, and a reporter at The Oneida Daily Dispatch. She has a BS in journalism.
Epigenetics is a hot topic at TCLF 2019
LA JOLLA, CALIF. –
In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.
Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.
Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.
And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. –
In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.
Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.
Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.
And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. –
In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.
Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.
Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.
And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Registry data favor CHOEP regimen for PTCL
LA JOLLA, CALIF. – Data from the Czech National Lymphoma Registry (NiHiL) suggest the CHOEP regimen (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) prolongs survival in newly diagnosed patients with peripheral T-cell lymphoma (PTCL), but consolidation with autologous stem cell transplant (ASCT) does not.
“We failed to show that there is a real benefit for the patient to undergo autologous stem cell consolidation, so, nowadays, in the majority of the centers in our group, CHOEP is the chemotherapy of choice, and the patients are not consolidated,” said Marek Trneny, MD, of Charles University General Hospital in Prague.
Dr. Trneny presented results from NiHiL on behalf of the Czech Lymphoma Study Group at the annual T-cell Lymphoma Forum.
The NiHiL project is a prospective, observational study (NCT03199066) of patients newly diagnosed with non-Hodgkin lymphoma in the Czech Republic.
Dr. Trneny presented data on 838 PTCL patients who were diagnosed between 1999 and 2018, 462 of whom were included in a survival analysis (1999-2016).
The 462 patients had a median age of 61 years and more than half were men.
Patients had PTCL not otherwise specified (NOS, 43.9%), Anaplastic lymphoma kinase (ALK)–negative Anaplastic large-cell lymphoma (ALCL, 20.8%), ALK-positive ALCL (7.6%), unclassified ALCL (0.9%), angioimmunoblastic T-cell lymphoma (AITL, 10.6%), and other subtypes (16.2%).
Most patients (79.1%) had tumors measuring less than 7.5 cm, about half of patients (52.3%) had B symptoms, most (70.5%) had a performance status of 0-1, and most (68.5%) had stage III-IV disease. Half of patients were low or low/intermediate risk according to the International Prognostic Index.
For the entire cohort, the median progression-free survival (PFS) was 1.15 years, and the 5-year PFS rate was 34.2%. The median overall survival (OS) was 2.83 years, and the 5-year OS rate was 43.3%.
There was no significant difference in PFS or OS for patients diagnosed from 1999 to 2007 and those diagnosed from 2008 to 2016. The median PFS was 1.05 years and 1.23 years, respectively (P= .4487), and the median OS was 2.15 years and 3.39 years, respectively (P = .176).
Patients with ALK-positive ALCL had superior PFS and OS when compared to patients with the other disease subtypes (P = .0002 for PFS and P = .0009 for OS).
Treatment comparison
When Dr. Trneny and his colleagues compared the 223 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and the 65 patients who received CHOEP, the researchers found that patients who received CHOEP had superior PFS and OS.
In the CHOP group, the median PFS was 1.18 years and the 5-year PFS rate was 34.2%. In the CHOEP group, the median PFS was 3.67 years and the 5-year PFS rate was 49.0% (hazard ratio, 0.6781; P = .0373).
In the CHOP group, the median OS was 3.74 years and the 5-year OS was 45.5%. In the CHOEP group, the median OS was 7.46 years and the 5-year OS was 56.4% (HR, 0.6475; P = .0381).
Dr. Trneny noted that patients who received CHOP were significantly younger (P less than .0001), more likely to have AITL or ALK-positive ALCL (P = .0152), and more likely to have a performance status of 2-4 (P = .0385).
Dr. Trneny and his colleagues also compared survival in 56 ASCT recipients and 189 patients who received chemotherapy alone (either CHOP or CHOEP).
Patients who underwent ASCT were significantly younger (P less than .0001) and more likely to have stage III or IV disease (P = .0345).
However, the researchers found no significant survival differences between patients who underwent ASCT and those who did not.
ASCT recipients had a median PFS of 7.50 years and a 5-year PFS rate of 56.0%, while patients who received chemotherapy alone had a median PFS of 4.69 years and a 5-year PFS rate of 47.3% (P = .6537).
In ASCT recipients, the median OS was not reached, and the 5-year OS rate was 63.3%. Among patients who received chemotherapy alone, the median OS was 6.78 years, and the 5-year OS was 63.0% (P = .6201).
“For those patients who are eligible for a CHOP-like regimen, CHOEP gives a higher chance for longer progression-free survival and overall survival, at least in our ... analysis,” Dr. Trneny said. “Autologous stem cell transplant, on the other hand, doesn’t seem to prolong PFS or overall survival.”
This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Data from the Czech National Lymphoma Registry (NiHiL) suggest the CHOEP regimen (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) prolongs survival in newly diagnosed patients with peripheral T-cell lymphoma (PTCL), but consolidation with autologous stem cell transplant (ASCT) does not.
“We failed to show that there is a real benefit for the patient to undergo autologous stem cell consolidation, so, nowadays, in the majority of the centers in our group, CHOEP is the chemotherapy of choice, and the patients are not consolidated,” said Marek Trneny, MD, of Charles University General Hospital in Prague.
Dr. Trneny presented results from NiHiL on behalf of the Czech Lymphoma Study Group at the annual T-cell Lymphoma Forum.
The NiHiL project is a prospective, observational study (NCT03199066) of patients newly diagnosed with non-Hodgkin lymphoma in the Czech Republic.
Dr. Trneny presented data on 838 PTCL patients who were diagnosed between 1999 and 2018, 462 of whom were included in a survival analysis (1999-2016).
The 462 patients had a median age of 61 years and more than half were men.
Patients had PTCL not otherwise specified (NOS, 43.9%), Anaplastic lymphoma kinase (ALK)–negative Anaplastic large-cell lymphoma (ALCL, 20.8%), ALK-positive ALCL (7.6%), unclassified ALCL (0.9%), angioimmunoblastic T-cell lymphoma (AITL, 10.6%), and other subtypes (16.2%).
Most patients (79.1%) had tumors measuring less than 7.5 cm, about half of patients (52.3%) had B symptoms, most (70.5%) had a performance status of 0-1, and most (68.5%) had stage III-IV disease. Half of patients were low or low/intermediate risk according to the International Prognostic Index.
For the entire cohort, the median progression-free survival (PFS) was 1.15 years, and the 5-year PFS rate was 34.2%. The median overall survival (OS) was 2.83 years, and the 5-year OS rate was 43.3%.
There was no significant difference in PFS or OS for patients diagnosed from 1999 to 2007 and those diagnosed from 2008 to 2016. The median PFS was 1.05 years and 1.23 years, respectively (P= .4487), and the median OS was 2.15 years and 3.39 years, respectively (P = .176).
Patients with ALK-positive ALCL had superior PFS and OS when compared to patients with the other disease subtypes (P = .0002 for PFS and P = .0009 for OS).
Treatment comparison
When Dr. Trneny and his colleagues compared the 223 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and the 65 patients who received CHOEP, the researchers found that patients who received CHOEP had superior PFS and OS.
In the CHOP group, the median PFS was 1.18 years and the 5-year PFS rate was 34.2%. In the CHOEP group, the median PFS was 3.67 years and the 5-year PFS rate was 49.0% (hazard ratio, 0.6781; P = .0373).
In the CHOP group, the median OS was 3.74 years and the 5-year OS was 45.5%. In the CHOEP group, the median OS was 7.46 years and the 5-year OS was 56.4% (HR, 0.6475; P = .0381).
Dr. Trneny noted that patients who received CHOP were significantly younger (P less than .0001), more likely to have AITL or ALK-positive ALCL (P = .0152), and more likely to have a performance status of 2-4 (P = .0385).
Dr. Trneny and his colleagues also compared survival in 56 ASCT recipients and 189 patients who received chemotherapy alone (either CHOP or CHOEP).
Patients who underwent ASCT were significantly younger (P less than .0001) and more likely to have stage III or IV disease (P = .0345).
However, the researchers found no significant survival differences between patients who underwent ASCT and those who did not.
ASCT recipients had a median PFS of 7.50 years and a 5-year PFS rate of 56.0%, while patients who received chemotherapy alone had a median PFS of 4.69 years and a 5-year PFS rate of 47.3% (P = .6537).
In ASCT recipients, the median OS was not reached, and the 5-year OS rate was 63.3%. Among patients who received chemotherapy alone, the median OS was 6.78 years, and the 5-year OS was 63.0% (P = .6201).
“For those patients who are eligible for a CHOP-like regimen, CHOEP gives a higher chance for longer progression-free survival and overall survival, at least in our ... analysis,” Dr. Trneny said. “Autologous stem cell transplant, on the other hand, doesn’t seem to prolong PFS or overall survival.”
This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Data from the Czech National Lymphoma Registry (NiHiL) suggest the CHOEP regimen (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) prolongs survival in newly diagnosed patients with peripheral T-cell lymphoma (PTCL), but consolidation with autologous stem cell transplant (ASCT) does not.
“We failed to show that there is a real benefit for the patient to undergo autologous stem cell consolidation, so, nowadays, in the majority of the centers in our group, CHOEP is the chemotherapy of choice, and the patients are not consolidated,” said Marek Trneny, MD, of Charles University General Hospital in Prague.
Dr. Trneny presented results from NiHiL on behalf of the Czech Lymphoma Study Group at the annual T-cell Lymphoma Forum.
The NiHiL project is a prospective, observational study (NCT03199066) of patients newly diagnosed with non-Hodgkin lymphoma in the Czech Republic.
Dr. Trneny presented data on 838 PTCL patients who were diagnosed between 1999 and 2018, 462 of whom were included in a survival analysis (1999-2016).
The 462 patients had a median age of 61 years and more than half were men.
Patients had PTCL not otherwise specified (NOS, 43.9%), Anaplastic lymphoma kinase (ALK)–negative Anaplastic large-cell lymphoma (ALCL, 20.8%), ALK-positive ALCL (7.6%), unclassified ALCL (0.9%), angioimmunoblastic T-cell lymphoma (AITL, 10.6%), and other subtypes (16.2%).
Most patients (79.1%) had tumors measuring less than 7.5 cm, about half of patients (52.3%) had B symptoms, most (70.5%) had a performance status of 0-1, and most (68.5%) had stage III-IV disease. Half of patients were low or low/intermediate risk according to the International Prognostic Index.
For the entire cohort, the median progression-free survival (PFS) was 1.15 years, and the 5-year PFS rate was 34.2%. The median overall survival (OS) was 2.83 years, and the 5-year OS rate was 43.3%.
There was no significant difference in PFS or OS for patients diagnosed from 1999 to 2007 and those diagnosed from 2008 to 2016. The median PFS was 1.05 years and 1.23 years, respectively (P= .4487), and the median OS was 2.15 years and 3.39 years, respectively (P = .176).
Patients with ALK-positive ALCL had superior PFS and OS when compared to patients with the other disease subtypes (P = .0002 for PFS and P = .0009 for OS).
Treatment comparison
When Dr. Trneny and his colleagues compared the 223 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and the 65 patients who received CHOEP, the researchers found that patients who received CHOEP had superior PFS and OS.
In the CHOP group, the median PFS was 1.18 years and the 5-year PFS rate was 34.2%. In the CHOEP group, the median PFS was 3.67 years and the 5-year PFS rate was 49.0% (hazard ratio, 0.6781; P = .0373).
In the CHOP group, the median OS was 3.74 years and the 5-year OS was 45.5%. In the CHOEP group, the median OS was 7.46 years and the 5-year OS was 56.4% (HR, 0.6475; P = .0381).
Dr. Trneny noted that patients who received CHOP were significantly younger (P less than .0001), more likely to have AITL or ALK-positive ALCL (P = .0152), and more likely to have a performance status of 2-4 (P = .0385).
Dr. Trneny and his colleagues also compared survival in 56 ASCT recipients and 189 patients who received chemotherapy alone (either CHOP or CHOEP).
Patients who underwent ASCT were significantly younger (P less than .0001) and more likely to have stage III or IV disease (P = .0345).
However, the researchers found no significant survival differences between patients who underwent ASCT and those who did not.
ASCT recipients had a median PFS of 7.50 years and a 5-year PFS rate of 56.0%, while patients who received chemotherapy alone had a median PFS of 4.69 years and a 5-year PFS rate of 47.3% (P = .6537).
In ASCT recipients, the median OS was not reached, and the 5-year OS rate was 63.3%. Among patients who received chemotherapy alone, the median OS was 6.78 years, and the 5-year OS was 63.0% (P = .6201).
“For those patients who are eligible for a CHOP-like regimen, CHOEP gives a higher chance for longer progression-free survival and overall survival, at least in our ... analysis,” Dr. Trneny said. “Autologous stem cell transplant, on the other hand, doesn’t seem to prolong PFS or overall survival.”
This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The 5-year progression free survival rate was 49.0% in the group receiving CHOEP, compared with 34.2% in the group receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone).
Study details: A survival analysis of 462 patients with PTCL who were part of the Czech National Lymphoma Registry.
Disclosures: This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
FDA approves new ALL treatment for children, young adults
The in pediatric and young adult patients aged 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.
Study participants received calaspargase pegol-mknl at 2,500 U/m2 (n = 118) or pegaspargase at 2,500 U/m2 (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m2 (n = 43) or 2,100 U/m2 (n = 68) or pegaspargase at 2,500 U/m2 (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.
The in pediatric and young adult patients aged 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.
Study participants received calaspargase pegol-mknl at 2,500 U/m2 (n = 118) or pegaspargase at 2,500 U/m2 (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m2 (n = 43) or 2,100 U/m2 (n = 68) or pegaspargase at 2,500 U/m2 (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.
The in pediatric and young adult patients aged 1 month to 21 years.
Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m2 given no more frequently than every 21 days.
The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m2 every 3 weeks.
Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.
Study participants received calaspargase pegol-mknl at 2,500 U/m2 (n = 118) or pegaspargase at 2,500 U/m2 (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.
Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.
The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m2 (n = 43) or 2,100 U/m2 (n = 68) or pegaspargase at 2,500 U/m2 (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.
Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.
FDA expands dasatinib indication to children with Ph+ ALL
The .
The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients aged 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Dasatinib is already approved for use in children aged 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).
In adults, dasatinib is approved to treat newly diagnosed, Ph+, chronic phase CML; chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL with resistance or intolerance to prior therapy. The approval in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).
In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol in patients (aged 1-17 years) with newly diagnosed, B-cell precursor, Ph+ ALL.
There were 78 patients evaluated for efficacy in cohort 1. They received dasatinib at a daily dose of 60 mg/m2 for up to 24 months.
Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.
The 3-year event-free survival rate in the 78 patients was 64.1%.
There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months.
The most common adverse events (AEs) in these patients were mucositis, febrile neutropenia, pyrexia, diarrhea, nausea, vomiting, musculoskeletal pain, abdominal pain, cough, headache, rash, fatigue, and constipation.
Eight patients (10%) had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.
Three patients (4%) had fatal AEs, all infections.
This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.
The .
The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients aged 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Dasatinib is already approved for use in children aged 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).
In adults, dasatinib is approved to treat newly diagnosed, Ph+, chronic phase CML; chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL with resistance or intolerance to prior therapy. The approval in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).
In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol in patients (aged 1-17 years) with newly diagnosed, B-cell precursor, Ph+ ALL.
There were 78 patients evaluated for efficacy in cohort 1. They received dasatinib at a daily dose of 60 mg/m2 for up to 24 months.
Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.
The 3-year event-free survival rate in the 78 patients was 64.1%.
There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months.
The most common adverse events (AEs) in these patients were mucositis, febrile neutropenia, pyrexia, diarrhea, nausea, vomiting, musculoskeletal pain, abdominal pain, cough, headache, rash, fatigue, and constipation.
Eight patients (10%) had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.
Three patients (4%) had fatal AEs, all infections.
This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.
The .
The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients aged 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Dasatinib is already approved for use in children aged 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).
In adults, dasatinib is approved to treat newly diagnosed, Ph+, chronic phase CML; chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL with resistance or intolerance to prior therapy. The approval in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).
In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol in patients (aged 1-17 years) with newly diagnosed, B-cell precursor, Ph+ ALL.
There were 78 patients evaluated for efficacy in cohort 1. They received dasatinib at a daily dose of 60 mg/m2 for up to 24 months.
Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.
The 3-year event-free survival rate in the 78 patients was 64.1%.
There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months.
The most common adverse events (AEs) in these patients were mucositis, febrile neutropenia, pyrexia, diarrhea, nausea, vomiting, musculoskeletal pain, abdominal pain, cough, headache, rash, fatigue, and constipation.
Eight patients (10%) had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.
Three patients (4%) had fatal AEs, all infections.
This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.
Checkmate 436: Two-drug combo is ‘promising’ for PMBCL
SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the annual meeting of the American Society of Hematology.
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.
The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.
SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.
SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the annual meeting of the American Society of Hematology.
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.
The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.
SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.
SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the annual meeting of the American Society of Hematology.
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.
The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.
SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The overall response rate was 70%, including a complete response rate of 27%.
Study details: A phase 1/2 study of 30 patients.
Disclosures: This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics, and investigators reported relationships with a range of other companies.
Source: Moskowitz AJ et al. ASH 2018, Abstract 1691.
ECHELON-2: BV-CHP boosts survival in PTCL
SAN DIEGO – A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to new research presented at the annual meeting of the American Society of Hematology.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS), compared with patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large cell lymphoma or other CD30-expressing PTCLs.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, with locations in New York and New Jersey.
Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.
Patients were randomized to receive BV-CHP plus placebo (n = 226) or CHOP plus placebo (n = 226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in the BV-CHP arm and the CHOP arm. The majority of patients were male – 59% in the BV-CHP arm and 67% in the CHOP arm – and most patients had stage III/IV disease, 81% and 80%, respectively.
In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (HR = 0.66, P = .0244).
Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.
BV-CHP had a safety profile comparable with that of CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
SOURCE: Horwitz S et al. ASH 2018, Abstract 997.
SAN DIEGO – A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to new research presented at the annual meeting of the American Society of Hematology.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS), compared with patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large cell lymphoma or other CD30-expressing PTCLs.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, with locations in New York and New Jersey.
Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.
Patients were randomized to receive BV-CHP plus placebo (n = 226) or CHOP plus placebo (n = 226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in the BV-CHP arm and the CHOP arm. The majority of patients were male – 59% in the BV-CHP arm and 67% in the CHOP arm – and most patients had stage III/IV disease, 81% and 80%, respectively.
In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (HR = 0.66, P = .0244).
Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.
BV-CHP had a safety profile comparable with that of CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
SOURCE: Horwitz S et al. ASH 2018, Abstract 997.
SAN DIEGO – A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to new research presented at the annual meeting of the American Society of Hematology.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS), compared with patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large cell lymphoma or other CD30-expressing PTCLs.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, with locations in New York and New Jersey.
Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.
Patients were randomized to receive BV-CHP plus placebo (n = 226) or CHOP plus placebo (n = 226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in the BV-CHP arm and the CHOP arm. The majority of patients were male – 59% in the BV-CHP arm and 67% in the CHOP arm – and most patients had stage III/IV disease, 81% and 80%, respectively.
In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (HR = 0.66, P = .0244).
Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.
BV-CHP had a safety profile comparable with that of CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
SOURCE: Horwitz S et al. ASH 2018, Abstract 997.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011), while the rate of death alone was 23% and 32%, respectively (HR = 0.66, P = .0244).
Study details: A phase 3 trial of 452 patients with peripheral T-cell lymphoma.
Disclosures: The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
Source: Horwitz S et al. ASH 2018, Abstract 997.
Phase 3 data support apixaban for cancer-associated VTE
SAN DIEGO – according to the Phase 3 ADAM VTE trial.
The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.
The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,
pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT) – 48% and 47%, respectively
- PE only – 44% and 39%, respectively
- PE with DVT – 12% in both arms
- DVT only – 37% and 35%, respectively
- Lower extremity DVT – 31% and 34%, respectively
- Upper extremity DVT – 17% and 14%, respectively
- Cerebral venous thrombosis (VT) – 1% and 0%, respectively
- Splanchnic VT – 8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).
“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
SOURCE: McBane RD et al. ASH 2018, Abstract 421.
SAN DIEGO – according to the Phase 3 ADAM VTE trial.
The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.
The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,
pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT) – 48% and 47%, respectively
- PE only – 44% and 39%, respectively
- PE with DVT – 12% in both arms
- DVT only – 37% and 35%, respectively
- Lower extremity DVT – 31% and 34%, respectively
- Upper extremity DVT – 17% and 14%, respectively
- Cerebral venous thrombosis (VT) – 1% and 0%, respectively
- Splanchnic VT – 8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).
“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
SOURCE: McBane RD et al. ASH 2018, Abstract 421.
SAN DIEGO – according to the Phase 3 ADAM VTE trial.
The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.
The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,
pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT) – 48% and 47%, respectively
- PE only – 44% and 39%, respectively
- PE with DVT – 12% in both arms
- DVT only – 37% and 35%, respectively
- Lower extremity DVT – 31% and 34%, respectively
- Upper extremity DVT – 17% and 14%, respectively
- Cerebral venous thrombosis (VT) – 1% and 0%, respectively
- Splanchnic VT – 8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).
“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
SOURCE: McBane RD et al. ASH 2018, Abstract 421.
REPORTING FROM ASH 2018
Key clinical point: Apixaban is associated with a similar risk of major bleeding and a lower risk of VTE recurrence when compared with dalteparin in patients with cancer-associated VTE.
Major finding: There were no major bleeding events in the apixaban arm and two in the dalteparin arm (P = .14).
Study details: Phase 3 study of 300 patients.
Disclosures: This study was funded by BMS/Pfizer Alliance.
Source: McBane RD et al. ASH 2018, Abstract 421.
FDA warns of serious side effect of AML treatment
The (Idhifa).
Enasidenib is FDA approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation. The drug is known to be associated with differentiation syndrome, and the drug’s prescribing information contains a boxed warning about this life-threatening condition.
However, the FDA has found that patients and health care providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.
The FDA also is warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).
However, the agency has not provided many details on cases related to this drug, which is FDA approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.
The agency is advising health care providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.
Symptoms of differentiation syndrome include:
- Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen.
- Pulmonary infiltrates and pleural effusion.
- Fever.
- Lymphadenopathy.
- Bone pain.
- Peripheral edema with rapid weight gain.
- Pericardial effusion.
- Hepatic, renal, and multiorgan dysfunction.
The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.If health care providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA. Providers also should monitor hemodynamics until improvement and provide supportive care as necessary.
If patients continue to experience renal dysfunction or severe pulmonary symptoms that require intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.
Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon. The FDA notes that in the clinical trial that supported approval of enasidenib at least 14% of patients experienced differentiation syndrome.
The manufacturer’s latest safety report includes five deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.
Differentiation syndrome was listed as the only cause of death in two cases. In the other cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.
One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly.
Treatment details are not available for the remaining three patients who died, according to the FDA.
The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n = 214) or ivosidenib (n = 179).
With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in two of the ivosidenib-treated patients (6%) and two of the enasidenib-treated patients (5%).
Additional results from this analysis are scheduled to be presented at the annual meeting of the American Society of Hematology (Abstract 288).
The (Idhifa).
Enasidenib is FDA approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation. The drug is known to be associated with differentiation syndrome, and the drug’s prescribing information contains a boxed warning about this life-threatening condition.
However, the FDA has found that patients and health care providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.
The FDA also is warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).
However, the agency has not provided many details on cases related to this drug, which is FDA approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.
The agency is advising health care providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.
Symptoms of differentiation syndrome include:
- Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen.
- Pulmonary infiltrates and pleural effusion.
- Fever.
- Lymphadenopathy.
- Bone pain.
- Peripheral edema with rapid weight gain.
- Pericardial effusion.
- Hepatic, renal, and multiorgan dysfunction.
The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.If health care providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA. Providers also should monitor hemodynamics until improvement and provide supportive care as necessary.
If patients continue to experience renal dysfunction or severe pulmonary symptoms that require intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.
Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon. The FDA notes that in the clinical trial that supported approval of enasidenib at least 14% of patients experienced differentiation syndrome.
The manufacturer’s latest safety report includes five deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.
Differentiation syndrome was listed as the only cause of death in two cases. In the other cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.
One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly.
Treatment details are not available for the remaining three patients who died, according to the FDA.
The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n = 214) or ivosidenib (n = 179).
With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in two of the ivosidenib-treated patients (6%) and two of the enasidenib-treated patients (5%).
Additional results from this analysis are scheduled to be presented at the annual meeting of the American Society of Hematology (Abstract 288).
The (Idhifa).
Enasidenib is FDA approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation. The drug is known to be associated with differentiation syndrome, and the drug’s prescribing information contains a boxed warning about this life-threatening condition.
However, the FDA has found that patients and health care providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.
The FDA also is warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).
However, the agency has not provided many details on cases related to this drug, which is FDA approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.
The agency is advising health care providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.
Symptoms of differentiation syndrome include:
- Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen.
- Pulmonary infiltrates and pleural effusion.
- Fever.
- Lymphadenopathy.
- Bone pain.
- Peripheral edema with rapid weight gain.
- Pericardial effusion.
- Hepatic, renal, and multiorgan dysfunction.
The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.If health care providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA. Providers also should monitor hemodynamics until improvement and provide supportive care as necessary.
If patients continue to experience renal dysfunction or severe pulmonary symptoms that require intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.
Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon. The FDA notes that in the clinical trial that supported approval of enasidenib at least 14% of patients experienced differentiation syndrome.
The manufacturer’s latest safety report includes five deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.
Differentiation syndrome was listed as the only cause of death in two cases. In the other cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.
One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly.
Treatment details are not available for the remaining three patients who died, according to the FDA.
The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n = 214) or ivosidenib (n = 179).
With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in two of the ivosidenib-treated patients (6%) and two of the enasidenib-treated patients (5%).
Additional results from this analysis are scheduled to be presented at the annual meeting of the American Society of Hematology (Abstract 288).
FDA approves gilteritinib for AML with FLT3 mutation
as detected by an FDA-approved test.
The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe, is used to detect the FLT3 mutation in patients with AML.
Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication and FLT3 tyrosine kinase domain.
The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial, which enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835 or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.
Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit. Efficacy results are available for 138 patients, with a median follow-up of 4.6 months.
The complete response (CR) rate was 11.6% (16/138), the CR rate with partial hematologic recovery (CRh) was 9.4% (13/138), and the CR/CRh rate was 21% (29/138). The median duration of CR/CRh was 4.6 months.
There were 106 patients who were transfusion dependent at baseline, and 33 of these patients (31.1%) became transfusion independent during the post-baseline period.
Seventeen of the 32 patients (53.1%) who were transfusion independent at baseline remained transfusion independent.
Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months.
The most common adverse events were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, constipation, stomatitis, cough, headache, hypotension, dizziness, and vomiting.
A total of 8% of patients (n = 22) discontinued gilteritinib because of adverse events, the most common of which were pneumonia (2%), sepsis (2%), and dyspnea (1%).
as detected by an FDA-approved test.
The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe, is used to detect the FLT3 mutation in patients with AML.
Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication and FLT3 tyrosine kinase domain.
The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial, which enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835 or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.
Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit. Efficacy results are available for 138 patients, with a median follow-up of 4.6 months.
The complete response (CR) rate was 11.6% (16/138), the CR rate with partial hematologic recovery (CRh) was 9.4% (13/138), and the CR/CRh rate was 21% (29/138). The median duration of CR/CRh was 4.6 months.
There were 106 patients who were transfusion dependent at baseline, and 33 of these patients (31.1%) became transfusion independent during the post-baseline period.
Seventeen of the 32 patients (53.1%) who were transfusion independent at baseline remained transfusion independent.
Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months.
The most common adverse events were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, constipation, stomatitis, cough, headache, hypotension, dizziness, and vomiting.
A total of 8% of patients (n = 22) discontinued gilteritinib because of adverse events, the most common of which were pneumonia (2%), sepsis (2%), and dyspnea (1%).
as detected by an FDA-approved test.
The FDA also expanded the approved indication for the LeukoStrat CDx FLT3 Mutation Assay to include use with gilteritinib. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe, is used to detect the FLT3 mutation in patients with AML.
Gilteritinib, developed by Astellas Pharma, has demonstrated inhibitory activity against FLT3 internal tandem duplication and FLT3 tyrosine kinase domain.
The FDA’s approval of gilteritinib was based on an interim analysis of the ADMIRAL trial, which enrolled adults with relapsed or refractory AML who had a FLT3 ITD, D835 or I836 mutation, according to the LeukoStrat CDx FLT3 Mutation Assay.
Patients received gilteritinib at 120 mg daily until they developed unacceptable toxicity or did not show a clinical benefit. Efficacy results are available for 138 patients, with a median follow-up of 4.6 months.
The complete response (CR) rate was 11.6% (16/138), the CR rate with partial hematologic recovery (CRh) was 9.4% (13/138), and the CR/CRh rate was 21% (29/138). The median duration of CR/CRh was 4.6 months.
There were 106 patients who were transfusion dependent at baseline, and 33 of these patients (31.1%) became transfusion independent during the post-baseline period.
Seventeen of the 32 patients (53.1%) who were transfusion independent at baseline remained transfusion independent.
Safety results are available for 292 patients. The median duration of exposure to gilteritinib in this group was 3 months.
The most common adverse events were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, constipation, stomatitis, cough, headache, hypotension, dizziness, and vomiting.
A total of 8% of patients (n = 22) discontinued gilteritinib because of adverse events, the most common of which were pneumonia (2%), sepsis (2%), and dyspnea (1%).
FDA approves rituximab biosimilar for lymphoma
(NHL).
Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.
Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.
Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.
The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”
Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).
(NHL).
Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.
Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.
Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.
The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”
Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).
(NHL).
Celltrion’s Truxima (rituximab-abbs) is a biosimilar of Genentech’s Rituxan (rituximab) and the first biosimilar approved in the United States to treat NHL.
Truxima (formerly CT-P10) is approved to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy. Truxima is approved as a single agent to treat relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL. Truxima is approved in combination with first-line chemotherapy to treat previously untreated follicular, CD20-positive, B-cell NHL.
Truxima is approved as single-agent maintenance therapy in patients with follicular, CD20-positive, B-cell NHL who achieve a complete or partial response to a rituximab product in combination with chemotherapy. Truxima also is approved as a single agent to treat nonprogressing, low-grade, CD20-positive, B-cell NHL after first-line treatment with cyclophosphamide, vincristine, and prednisone.The label for Truxima contains a boxed warning detailing the risk of fatal infusion reactions, severe skin and mouth reactions (some with fatal outcomes), hepatitis B virus reactivation that may cause serious liver problems (including liver failure and death), and progressive multifocal leukoencephalopathy.
The FDA said its approval of Truxima is “based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrates Truxima is biosimilar to Rituxan.”
Findings from a phase 3 trial suggested that Truxima is equivalent to the reference product in patients with low-tumor-burden follicular lymphoma (Lancet Haematol. 2018 Nov;5[11]:e543-53).