Intensive Chemotherapy Plus Venetoclax Yielded High CRc, MRD Negativity in AML

Adding the BCL2 inhibitor venetoclax to intensive chemotherapy with cladribine, idarubicin, and cytarabine resulted in deep and durable remissions in young, fit patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), according to phase 2 study results (Abstract 734) presented at the American Society of Hematology Annual Meeting.

More than 90% of patients treated with the regimen achieved a composite complete response (CRc), with more than 80% of those with AML and a CRc achieving minimal residual disease (MRD)–negative status.

“We think that CLIA-venetoclax is a highly effective and potentially curative regimen, producing deep and durable remissions in [newly diagnosed MDS and AML],” said study presenter Tapan Kadia, MD, of the University of Texas, MD Anderson Cancer Center.

The study included 95 patients aged 65 or younger diagnosed with AML, mixed phenotype acute leukemia, high-risk MDS, or myeloid blast phase chronic myeloid leukemia (CML). Patients were given cladribine, cytarabine, idarubicin, and venetoclax. If remission was achieved, patients could receive up to five additional cycles of dose-attenuated consolidation.

The overall response rate was 96%. Looking only at patients with AML, the overall response rate was 95%, with 94% achieving CRc. Eighty-nine percent of patients who achieved CRc were MRD negative.

Patients were followed  up for a median of 2.9 years. Among patients with AML, the estimated 2-year overall survival rate was 75%, decreasing to 73% at year five. The relapse-free survival was 76% at two years and 74% at five years. Among patients with MDS, the estimated two- and five-year overall survival was 100%.

For the 69% of patients with AML who proceeded to stem cell transplantation in first remission, the two-year overall survival was 84% and the five-year overall survival was 82% compared with 63%  for those who did not undergo transplant.

All patients with AML had grade 3 or worse anemia, neutropenia, and thrombocytopenia. One death occurred within 30 days and two deaths occurred within 60 days.

“The first patient was treated on this protocol more than six years ago. As of today, 75 of the 96 patients are still alive,” Dr. Kadia said.

Kadia reported relationships with Rigel, Novartis, Amgen, Incyte, DrenBio, ASTEX, Regeneron, Ascentage, Abbvie, JAZZ, Cellenkos, AstraZeneca, BMS, Pfizer, Genentech, Sellas, and Servier.

REFERENCE:

Bouligny IM, Kantarjian HM, Yilmaz M, et al. A phase II trial of venetoclax in combination with cladribine, idarubicin, and cytarabine in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Abstract #734. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.