Work

Oral Azacitidine Use after Stem Cell Transplantation for Myeloid Malignancies: A Single Center Experience

Year: 2025

Type: article

Abstract: Background Relapse is the main cause of treatment failure following allogeneic HSCT in patients (pts) with acute myeloid leukemia (AML). Oral-AZA demonstrated post-HSCT immunomodulatory activity, resulting in low relapse rates in pts with morphologic complete remission (mCR) in a phase 1/2 trial (ASBMT 2018). In this retrospective study, we describe our experience with post-HSCT Oral-AZA maintenance. Methods We analyzed 28 adult pts with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML) who received HSCT from 5/2018 to 2/2024 at The Ohio State University, who were in mCR post-HSCT, and had received ≥1 cycle of Oral-AZA. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Measurable residual disease (MRD) was considered positive at any detectable level of residual disease . Results The median age was 62.5 y (21–75 y). Nineteen (68%) pts had AML, 7 (25%) MDS, and 2 (7%) CMML. Fourteen (50%) had very high/high-risk disease (by ELN 2022, Molecular International Prognostic Scoring System [IPSS-M], CMML-specific prognostic scoring system [CPSS] scores, respectively); TP53 mutation was present in 3 pts (11%) and complex karyotype were present in 4 pts (14 %); 1 (4%) pt had both TP53 mutation and complex karyotype . Six (21%) pts had active disease before HSCT, 23 (82%) received matched unrelated donor, and 20 (71%) received reduced-intensity conditioning. Fourteen (50%) pts were MRD positive before HSCT, but all pts were MRD negative after HSCT and before starting Oral-AZA. Oral-AZA was initiated a median of 80 d post-HSCT (44–209 d), with a median of 6.5 cycles (1–18 cycles); 50% received a 6–10-d course of therapy ( Figure 1A ). Twenty-seven (96%) pts received 200 mg Oral-AZA daily and one pt received 300 mg daily. At a median follow-up of 11.4 mo (4.1–32.4 mo), 1-y and 2-y OS rates were 100% and 79%, and RFS rates were 95% and 70%, respectively ( Figure 1B ). Three (11%) pts who relapsed while on maintenance received Oral-AZA daily in 28-d cycles as follows: 200 mg for 7 d (8 cycles); 300 mg for 3 d (3 cycles); and 200 mg for 5 d (10 cycles). One (4%) pt who received 8 cycles of Oral-AZA had a complex karyotype, none had TP53 mutation. Oral-AZA was discontinued in 10 pts (36%) due to relapse (n=3), graft-versus-host disease (n=3), gastrointestinal toxicity (n=2), and other reasons (n=2). Conclusion Maintenance with Oral-AZA post-allogeneic HSCT is feasible, fairly well-tolerated, and the encouraging 1-y survival outcomes despite high-risk disease factors warrant further research to estimate long-term clinical benefits. The randomized study AMADEUS (NCT04173533), examining the efficacy of Oral-AZA following HSCT, may provide additional insights in this area of unmet need.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.659