User login
© Todd Buchanan 2016
SAN DIEGO—A targeted therapy combined with standard chemotherapy can produce rapid, deep remissions in patients with newly diagnosed acute myeloid leukemia (AML), according to research presented at the 2016 ASH Annual Meeting.
In this phase 1b study, investigators tested vadastuximab talirine, an antibody drug conjugate targeting CD33, in combination with 7+3 chemotherapy—a continuous infusion of cytarabine for 7 days plus daunorubicin for 3 days.
The combination produced a high rate of response, which included minimal residual disease (MRD)-negative complete remissions (CRs).
The treatment also resulted in “acceptable” on-target myelosuppression and non-hematologic adverse events (AEs) similar to what would be expected with 7+3 alone, according to study investigator Harry Erba, MD, PhD, of the University of Alabama at Birmingham.
Dr Erba presented these results in abstract 211.* The research was sponsored by Seattle Genetics, Inc.
The study included 42 newly diagnosed AML patients with a median age of 45.5. Half the patients had intermediate-risk karyotypes, 36% had adverse karyotypes, and 17% had secondary AML.
Patients received escalating doses of vadastuximab talirine (10+10 mcg/kg [n=4] and 20+10 mcg/kg [n=38]) in combination with 7+3 induction (cytarabine at 100 mg/m2 and daunorubicin at 60 mg/m2) on days 1 and 4 of a 28-day treatment cycle. Responses were assessed on days 15 and 28.
A second induction regimen and post-remission therapies were prescribed according to investigator choice and did not include vadastuximab talirine.
Results
The maximum tolerated dose of vadastuximab talirine was 20+10 mcg/kg.
Hematologic treatment-related AEs included febrile neutropenia (43%, grade 1-3), thrombocytopenia (38%, grade 3-4), anemia (24%, grade 3), and neutropenia (17%, grade 3-4).
Non-hematologic treatment-related AEs included nausea (17%), fatigue (14%), diarrhea (7%), and decreased appetite (7%). All of these AEs were grade 1-2.
None of the patients experienced infusion-related reactions, veno-occlusive disease, or significant liver damage.
A total of 76% of patients responded to treatment, with 60% percent achieving a CR and 17% achieving a CR with incomplete blood count recovery (CRi).
The 76% response rate is close to what would be expected for a well-chosen population fit for a clinical trial, Dr Erba said.
There was a hint of additional benefit as well, he added.
“The first hint was that 30 out of the 32 patients [who achieved a CR/CRi] required only 1 round of chemotherapy to achieve that remission,” Dr Erba said. “This also suggested that deeper remissions may be possible.”
MRD assessments using a sensitive flow cytometric assay revealed that 25 of the 32 patients (78%) who achieved a CR/CRi were MRD-negative.
Dr Erba said a randomized, phase 2 trial of vadastuximab talirine plus 7+3 versus 7+3 alone is planned for the first quarter of 2017. 
*Information presented at the meeting differs from the abstract.
© Todd Buchanan 2016
SAN DIEGO—A targeted therapy combined with standard chemotherapy can produce rapid, deep remissions in patients with newly diagnosed acute myeloid leukemia (AML), according to research presented at the 2016 ASH Annual Meeting.
In this phase 1b study, investigators tested vadastuximab talirine, an antibody drug conjugate targeting CD33, in combination with 7+3 chemotherapy—a continuous infusion of cytarabine for 7 days plus daunorubicin for 3 days.
The combination produced a high rate of response, which included minimal residual disease (MRD)-negative complete remissions (CRs).
The treatment also resulted in “acceptable” on-target myelosuppression and non-hematologic adverse events (AEs) similar to what would be expected with 7+3 alone, according to study investigator Harry Erba, MD, PhD, of the University of Alabama at Birmingham.
Dr Erba presented these results in abstract 211.* The research was sponsored by Seattle Genetics, Inc.
The study included 42 newly diagnosed AML patients with a median age of 45.5. Half the patients had intermediate-risk karyotypes, 36% had adverse karyotypes, and 17% had secondary AML.
Patients received escalating doses of vadastuximab talirine (10+10 mcg/kg [n=4] and 20+10 mcg/kg [n=38]) in combination with 7+3 induction (cytarabine at 100 mg/m2 and daunorubicin at 60 mg/m2) on days 1 and 4 of a 28-day treatment cycle. Responses were assessed on days 15 and 28.
A second induction regimen and post-remission therapies were prescribed according to investigator choice and did not include vadastuximab talirine.
Results
The maximum tolerated dose of vadastuximab talirine was 20+10 mcg/kg.
Hematologic treatment-related AEs included febrile neutropenia (43%, grade 1-3), thrombocytopenia (38%, grade 3-4), anemia (24%, grade 3), and neutropenia (17%, grade 3-4).
Non-hematologic treatment-related AEs included nausea (17%), fatigue (14%), diarrhea (7%), and decreased appetite (7%). All of these AEs were grade 1-2.
None of the patients experienced infusion-related reactions, veno-occlusive disease, or significant liver damage.
A total of 76% of patients responded to treatment, with 60% percent achieving a CR and 17% achieving a CR with incomplete blood count recovery (CRi).
The 76% response rate is close to what would be expected for a well-chosen population fit for a clinical trial, Dr Erba said.
There was a hint of additional benefit as well, he added.
“The first hint was that 30 out of the 32 patients [who achieved a CR/CRi] required only 1 round of chemotherapy to achieve that remission,” Dr Erba said. “This also suggested that deeper remissions may be possible.”
MRD assessments using a sensitive flow cytometric assay revealed that 25 of the 32 patients (78%) who achieved a CR/CRi were MRD-negative.
Dr Erba said a randomized, phase 2 trial of vadastuximab talirine plus 7+3 versus 7+3 alone is planned for the first quarter of 2017.
*Information presented at the meeting differs from the abstract.
© Todd Buchanan 2016
SAN DIEGO—A targeted therapy combined with standard chemotherapy can produce rapid, deep remissions in patients with newly diagnosed acute myeloid leukemia (AML), according to research presented at the 2016 ASH Annual Meeting.
In this phase 1b study, investigators tested vadastuximab talirine, an antibody drug conjugate targeting CD33, in combination with 7+3 chemotherapy—a continuous infusion of cytarabine for 7 days plus daunorubicin for 3 days.
The combination produced a high rate of response, which included minimal residual disease (MRD)-negative complete remissions (CRs).
The treatment also resulted in “acceptable” on-target myelosuppression and non-hematologic adverse events (AEs) similar to what would be expected with 7+3 alone, according to study investigator Harry Erba, MD, PhD, of the University of Alabama at Birmingham.
Dr Erba presented these results in abstract 211.* The research was sponsored by Seattle Genetics, Inc.
The study included 42 newly diagnosed AML patients with a median age of 45.5. Half the patients had intermediate-risk karyotypes, 36% had adverse karyotypes, and 17% had secondary AML.
Patients received escalating doses of vadastuximab talirine (10+10 mcg/kg [n=4] and 20+10 mcg/kg [n=38]) in combination with 7+3 induction (cytarabine at 100 mg/m2 and daunorubicin at 60 mg/m2) on days 1 and 4 of a 28-day treatment cycle. Responses were assessed on days 15 and 28.
A second induction regimen and post-remission therapies were prescribed according to investigator choice and did not include vadastuximab talirine.
Results
The maximum tolerated dose of vadastuximab talirine was 20+10 mcg/kg.
Hematologic treatment-related AEs included febrile neutropenia (43%, grade 1-3), thrombocytopenia (38%, grade 3-4), anemia (24%, grade 3), and neutropenia (17%, grade 3-4).
Non-hematologic treatment-related AEs included nausea (17%), fatigue (14%), diarrhea (7%), and decreased appetite (7%). All of these AEs were grade 1-2.
None of the patients experienced infusion-related reactions, veno-occlusive disease, or significant liver damage.
A total of 76% of patients responded to treatment, with 60% percent achieving a CR and 17% achieving a CR with incomplete blood count recovery (CRi).
The 76% response rate is close to what would be expected for a well-chosen population fit for a clinical trial, Dr Erba said.
There was a hint of additional benefit as well, he added.
“The first hint was that 30 out of the 32 patients [who achieved a CR/CRi] required only 1 round of chemotherapy to achieve that remission,” Dr Erba said. “This also suggested that deeper remissions may be possible.”
MRD assessments using a sensitive flow cytometric assay revealed that 25 of the 32 patients (78%) who achieved a CR/CRi were MRD-negative.
Dr Erba said a randomized, phase 2 trial of vadastuximab talirine plus 7+3 versus 7+3 alone is planned for the first quarter of 2017.
*Information presented at the meeting differs from the abstract.