Outcomes of Adults With Relapsed/Refractory Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center

Abstract

Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using venetoclax in combination with decitabine or azacitidine, which is not otherwise widely evaluated in the current literature. Our patients come from a large, socioeconomically and geographically diverse area including the majority of Northern California. Most had ELN Adverse Risk (52%) or Intermediate Risk (44%) AML, and most had an ECOG Performance Status of 1 (64%). Over half (52%) had prior hypomethylating agent exposure, and 40% had Secondary AML. We observed an overall response rate of 52%, with eight patients (32%) achieving composite complete remission. Median overall survival was 5.5 months, and for patients achieving composite complete remission this was 21.6 months. One-year estimated overall survival was 38%. Three patients were able to proceed directly to stem cell transplant for consolidation, and all three were alive at last follow-up, ranging 13.8-24.0 months. We found venetoclax in combination with hypomethylating agents to be well tolerated and potentially efficacious in securing long-term remissions for patients with relapsed/refractory AML.

Keywords: acute myeloid leukemia; hypomethylating agent; real-world data; relapsed/refractory; venetoclax (BCL-2 inhibitor).

Figure 1

(A) Top: Response types to therapy are shown for the overall population and several subgroups with specific risk factors. No significant differences were seen between different risk groups ( Table 1 ). Overall, 4 had CR (16%), 4 Cri (16%), and 5 MLFS (20%), for an ORR 52%. (B) Middle: Kaplan-Meier survival estimates are shown. A median follow-up of 14.6 months was seen (calculated by reverse-Kaplan-Meier). Median Overall Survival (OS) for the whole population was 5.5 (95% Cl, 2.9-21.6) months. Median OS for patients achieving cCR was 21.6 (95% Cl, 15.2-Not Reached) months, which was significantly longer than for those achieving MLFS at 4.4 (95% Cl, 2.4-6.6) months or no response at 3.0 (95% Cl, 0.8-5.8) months (Log-rank Chi² 11.62, p<0.009). One-year estimated OS was 38% for the entire population (95% Cl, 18.4% - 57.5%). (C) Bottom: Median OS for patients who were HMA-naïve is compared to those with prior HMA use. The HMA-naïve group had a median OS of 21.6 (95% Cl, 1.3-Not Reached) months compared to 4.3 (95% Cl, 1.3-6.6) months for those with prior exposure either for MDS treatment (n=2) or prior AML treatment (n=10) (HR=0.40, 95% Cl=0.15 to 1.07.)