Combining standard chemotherapy with vadastuximab talirine was safe and well-tolerated in newly diagnosed acute myeloid leukemia.
Combining standard chemotherapy with the CD33-directed antibody conjugate vadastuximab talirine (33A) was safe and well-tolerated in patients with newly diagnosed acute myeloid leukemia (AML), according to the results of a phase Ib study (abstract 211) presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition, held December 3–6 in San Diego, California.
Early efficacy results from the trial were also encouraging, according to Harry Erba, MD, PhD, of the University of Alabama at Birmingham, with 30 out of 32 patients who achieved complete remission achieving it after a single round of therapy.
“That might not be something that leads to FDA approval or registration, but it is really important for a patient who cares about the difference of being in the hospital for 4 weeks vs 6 to 8 weeks if they get 2 cycles,” Dr. Erba said during a press conference.
According to Dr. Erba, the standard treatment for AML is continuous infusion of cytarabine for 7 days plus infusion with an anthracycline for 3 days, a regimen called 7+3. This regimen has been in use for about 4 decades but achieves a remission rate of only about 40% to 50% in patients younger than 60 years.
33A is a CD33-directed antibody conjugate; CD33 is a protein found in about 90% of patients with AML. This phase Ib study included 42 patients who were administered 33A in escalating doses combined with 7+3 induction therapy (cytarabine 100 mg/m2 and daunorubicin 60 mg/m2). 33A was given in combination with 7+3 on days 1 and 4 of a 28-day cycle, and response assessments occurred on days 15 and 28.
There was no evidence of increased toxicity or mortality and the rates of adverse events seen on the study were similar to those expected with standard chemotherapy alone, according to Dr. Erba. There were no infusion-related reactions, veno-occlusive disease, or significant hepatotoxicity.
Overall, the composite complete remission rate was 76%. Complete remission occurred in 60% of patients, and an additional 17% of patients had complete remission with incomplete hematologic recovery. When the data were broken down by cytogenetic risk group, there was a lower overall response in patients with adverse risk (60%); however, Dr. Erba said that it still “compares favorably with what we might expect for historical controls for the cytogenetic group.”
Overall, 94% of complete remissions occurred within the first cycle of therapy. According to Dr. Erba, this “suggested that we might be getting deeper remissions.” To explore that further, the researchers used 10 color multi-parameter flow cytometry to evaluate response. They found that 78% of patients who attained composite complete remissions achieved minimal residual disease negative status.
Dr. Erba said that this regimen will be evaluated further in a randomized phase II trial comparing 7+3 with or without 33A.