Venetoclax-Based Salvage Therapy for Post-Hematopoietic Cell Transplantation Relapse in Acute Myeloid Leukemia

Introduction: AML pts who relapse after allogeneic hematopoietic cell transplantation (HCT) face poor clinical outcomes and short overall survival (OS) (Schmid et al, Blood2012). The delivery of optimal salvage therapy is challenging as some pts do not tolerate high intensity regimens, and lower intensity therapies may not yield sufficient disease control. Favorable responses in older, treatment naïve AML pts with venetoclax (VEN) in combination with low-dose cytarabine (LDAC) or DNA methyltransferase inhibitor (DNMTi) led to its approval. Off-label use in relapsed/refractory AML is increasing (DiNardo et al, Am J Hematol2018; Aldoss et al, Haematologica2018). We retrospectively evaluated the overall response rate (ORR = CR+CRi+PR+MLFS) and report our clinical experience with VEN-based salvage in post-HCT relapsed AML. Methods: After IRB approval, consecutive pts with post-HCT relapsed AML treated with VEN+LDAC or VEN+DNMTi from May 2018 to July 2019 were retrospectively analyzed. Selection of VEN partner and dosing were at the discretion of the treating physician based on institutional guidelines and published prescribing information. Responses were assigned based on the AML IWG criteria. The Kaplan-Meier method was used to describe OS. ORR and treatment complications were summarized via descriptive statistics. Results: 18 pts with post-HCT relapsed AML who received at least 1 cycle of VEN-based salvage chemotherapy were included. Median age at HCT was 64.5 years (range 34.5-73.7 years). Most pts were poor risk: 6/18 pts had an antecedent hematologic malignancy, 12/18 had an abnormal or complex karyotype (CK) prior to HCT, and 4/12 pts with CK also were TP53mut. 15/18 (83.3%) received reduced intensity conditioning and MUD was the predominant graft type (50%). All pts received PBSCs. Additional disease and response characteristics are reported in Fig 1A. Median time from HCT to relapse was 5.5 mos (range: 0.9 to 44.9 mos); 27.8% of pts relapsed within 100 days and 55.6% relapsed within 6 mos of HCT. At relapse, 1 patient had grade 2 aGVHD and 1 had severe, extensive cGVHD. No pts experienced a GVHD flare or progression during treatment. 14/18 (77.8%) of pts were receiving immunosuppressive therapy (IST) at relapse and received VEN concurrently with IST. VEN-based salvage chemotherapy began shortly after confirmed relapse (range: 4-46 days); 4/18 pts received VEN with LDAC and 14/18 were treated with a DNMTi partner. 15/18 pts were evaluable for response.