P500: superior outcomes after allogeneic stem cell transplantation among patients ≥ 60 years treated with cladribine, low dose cytarabine plus venetoclax for newly diagnosed acute myeloid leukemia

Background: A low intensity regimen consisting of Cladribine (CLAD), Low dose cytarabine (LDAC) and Venetoclax (VEN) alternating with Azacitidine (AZA) and VEN has shown promising outcomes in older patients (pts) with acute myeloid leukemia (AML) (Kadia et al, JCO Nov 2022). Improved disease control and preserved performance status achieved with CLAD/LDAC/VEN treatment, may translate into superior post-stem cell transplantation (SCT) outcomes. Aims: We aimed to study the outcomes of older pts with AML who underwent SCT post CLAD-LDAC-VEN therapy and compare to those who underwent SCT after hypomethylating agent (HMA)-VEN based or intensive (INT) therapy. Methods: Pts ≥ 60 yrs of age treated on the phase II study of CLAD-LDAC-VEN (NCT03586609) who underwent SCT in 1st remission (CR1) were compared to a retrospective cohort of pts ≥ 60 yrs treated with HMA-VEN based or INT therapy who underwent SCT in CR1 between 2013-2022. Relapse free survival (RFS) was from response to relapse/death and overall survival (OS) from start of therapy to death. We performed competing event analysis to study the cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) for the patients on these 3 treatment arms. Results: 35 pts treated with CLAD-LDAC-VEN were compared to 40 pts treated with HMA-VEN & 42 pts with INT therapy for remission induction prior to SCT at our center (Figure 1). The median age of pts in the low-intensity arms were similar (68 yrs), but lower on the INT arm (62 yrs). More pts post-INT therapy received a myeloablative conditioning (MAC). At a median follow up of 17+ mos for CLAD-LDAC-VEN arm, 30 mos for HMA arm, and 59 mos for INT arm the median RFS (NR vs. 20 mos vs. 50 mos respectively, p <0.01) and OS (NR vs. 32 m vs. 58 m respectively, p < 0.01) was superior for the CLAD-LDAC-VEN arm. 3-yr cumulative incidence of relapse & NRM (as competing events) were both significantly lower with CLAD-LDAC-VEN (4% and 7%) compared to HMA-VEN (41% and 27%) or INT therapy (17% and 23%) (Figure 1). The rates of any-grade acute graft versus host disease (GVHD) was slightly lower in the CLAD-LDAC-VEN arm (34%) compared to HMA (54%) and INT arms (67%); 31/35 pts (88%) in the CLAD-LDAC-VEN arm had received post-transplant cyclophosphamide GVHD prophylaxis compared to 35/40 (87%) pts in HMA arm (p- 0.99) and 25/42 (60%) pts in the INT arm (p- 0.005). Summary/Conclusion: Older pts with AML proceeding to SCT after CLAD-LDAC-VEN therapy had significantly improved survival, characterized by significantly lower rates of NRM and relapse compared to HMA-VEN or INT therapies. Larger studies and longer follow up is needed to further confirm its benefit.Keywords: Cladribine, Acute myeloid leukemia, Venetoclax, Allogeneic hematopoietic stem cell transplant