Venetoclax Combination as Induction Therapy in AML and MDS

First-line induction therapy with cladribine, idarubicin, and cytarabine plus venetoclax (CLIA-venetoclax) achieved high rates of complete response (CR) and measurable residual disease (MRD) negativity among patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to a report at the 66th American Society of Hematology Annual Meeting & Exposition.

“High complete response rates and low early mortality rates facilitate the majority of patients to allogeneic stem cell transplant (SCT),” added presenting author, Tapan Kadia, MD, of the University of Texas MD Anderson Cancer Center.

The phase II trial included 95 patients, of which 85 (90%) had AML, three (3%) had mixed phenotype acute leukemia (MPAL), and seven (7%) had MDS. The median age at diagnosis in the AML and MDS groups was 49 years (range, 18–64) and 46 years (range, 36–58), respectively.

The composite CR (CRc) rate was 93%, with a CR rate of 84% and CR with incomplete count recovery (CRi) rate of 8%. One patient with MDS had hematologic improvement, and one patient with AML had a partial response. Altogether, the overall response rate was 95%. Among patients with AML with CR or CRi, the rate of negative MRD status was 82%.

The authors estimated the probability of OS and relapse-free survival (RFS) per disease subgroup at the following timepoints.

A total of 65 patients with AML underwent allogeneic SCT in first remission. In what the authors called a “landmark analysis,” they reported that 1-year and 2-year OS after SCT was 88% and 82%, respectively, for patients who received CLIA-venetoclax compared with 82% and 59%, respectively, for patients who did not receive CLIA-venetoclax.

“CLIA-venetoclax is a highly effective regimen, producing deep and durable remissions in patients with newly diagnosed AML,” Dr. Kadia and colleagues summarized.

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 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.