ASH 2024 | CLIA plus venetoclax in younger patients with newly diagnosed AML and HR-MDS

In the Phase II CLIA venetoclax trial, we enrolled younger fit patients with newly diagnosed AML or higher-risk MDS to receive intensive chemotherapy with venetoclax. The intensive chemotherapy backbone was CLIA, which was cladribine 5 mg per m2 for 5 days, idarubicin 8-10 mg per m2 for 3 days, and cytarabine 1-1.5 g per m2 for 5 days, in combination with the BCL2 inhibitor venetoclax, 400 milligrams per day for seven days, which we adjusted accordingly for antifungal prophylaxis. In the consolidation cycles, we reduced the dose and duration of chemotherapy. We gave cladribine and cytarabine for three days, idarubicin for two days, and we kept the venetoclax at 400 milligrams for seven days. In the updated analysis, we treated 89 patients with AML and seven patients with MDS. The median age was 49 years, reflecting a younger cohort, and most patients with AML were ELN 2022 adverse risk. The composite complete remission rate among patients with AML was 94%. The rate of MRD negativity by multi-parameter flow cytometry among patients in remission was 89%. The overall response rate among the ELN 2022 risk categories was 100% for favorable risk, 96% for intermediate risk, and 92% for adverse risk AML. So next, we look at the molecular categories. And among 30 patients with NPM1 mutated AML, the overall response rate was 100%. And among 12 patients with KMT2A rearrangements, the overall response rate was 100%. And lastly, in seven patients with higher-risk MDS, the overall response rate was also 100%. So patients received a median of two cycles of therapy, and nearly 70% of patients with AML underwent stem cell transplant. So this approach translated to an outstanding overall survival in AML and MDS. In patients with AML, the two-year overall survival was 75%, and the five-year overall survival was 73%. In patients with MDS, the two and five-year overall survival was 100%. So taken together, the composite complete remission rate of CLIA-venetoclax in AML was 94% with a majority, about 90% of patients attaining an MRD negative response. And these very high response rates facilitated most patients to transplant and low relapse rates after transplant translated to an exceptional five-year overall survival rates. So CLIA-venetoclax appears to be a highly effective curative regimen that produces deep and durable remissions for AML and for high-risk MDS.

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