Hypomethylating Agents and Low-Dose Venetoclax for Relapse Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation

Background Relapse of Acute Myeloid Leukemia (AML) after allogeneic stem cell transplantation (AlloSCT) is a major cause of treatment failure. Several approaches like modifications of conditioning regimens and lately maintenance had failed to reduce the risk of recurrence. Some rescue strategies like decreasing the immunosuppression therapies, donor lymphocyte infusions and salvage chemotherapies had limited responses and aren't exempt of toxicities. Venetoclax (VEN) is a novel small molecule inhibitor of the anti-apoptotic protein BCL-2. Combinations with hypomethylating agents (HMAs) in treatment naive elderly patients (pts) had led overall responses (CR+Cri+PR) of 67% (Dinardo, Blood 2017). Single-agent activity in relapsed and refractory (R/R) AML as well as in combinations had demonstrated objective responses of 21%. Experience is limited after Allo SCT. Therefore, we evaluated the overall response rate (ORR = CR+CRi+PR) and report our clinical experience with low-dose VEN-based salvage in post-AlloSCT in relapsed AML pts. Methods All relapsed AML post Allo SCT pts treated with low-dose VEN+HMAs from July 2018 to July 2019, who received at least 1 cycle of VEN-based salvage chemotherapy were included. Responses were assigned based on the AML IWG criteria. ORR and treatment complications were summarized. Results A total of 9 pts with relapsed AML after Allo SCT received either decitabine 20mg/m2 day 1-5 (8 pts) or Azacitidine 75mg/m2 IV for 7 days and low-dose VEN at ramp up dose to 100mg. Median age at AlloSCT was 55.7 years (range 32-73 years). Most pts had poor risk features. 4/9 pts had complex karyotype at relapse and 55% pts were TP53mut. Median time from transplant to relapse was 11 months (range: 2 to 45 months); 44% of pts relapsed within 100 days and 55% of pts were receiving immunosuppressive therapy (IST) at time of relapse. Objective response was observed in 4(44%) pts, including 3 CRi which all were achieved after the first cycle. One patient achieved CRi and cleared a TP53 mutation. The other pts were diploid cytogenetics with presence of FLT3-ITD and the other with presence of t (9;11). Conclusion HMAs and Low-Dose VEN is viable salvage therapy option, even after heavily treated patients including after AlloSCT. Responses are significant even in lower-dose venetoclax with minimal toxicities. This combination is safe and efficacious thus further exploration in a larger cohort will be necessary.