Revumenib as maintenance for AML following allogeneic stem cell transplantation.

Abstract

6505 Background: Relapse after allogeneic stem cell transplantation (SCT) remains common in acute myeloid leukemia (AML). Revumenib is approved for relapsed/refractory (R/R) NPM1 mt or KMT2A r acute leukemia however its safety and efficacy as post-SCT maintenance has not been characterized. We report outcomes of revumenib maintenance post-SCT in adult and pediatric patients (pts) at our institution. Methods: Pts with NPM1 mt, KMT2A r or NUP98 r AML could continue post-SCT revumenib maintenance following response pre-SCT to revumenib monotherapy or combination on clinical trial. Revumenib was resumed at pre-SCT dose with adjustment for azoles. Results: Twenty-one pts were included (11 adult, 10 pediatric); median age 20 years (range, 1 – 69), 62% female. Most (n = 16, 76%) had KMT2A r, 4 (19%) had NPM1 mt, and 1 peds pt had NUP98 r. Pre-SCT, revumenib was given as monotherapy per AUGMENT-101 (NCT04065399, n = 8) or Expanded Access (NCT05918913, n = 2) or with oral decitabine and venetoclax per SAVE (NCT05360160, n = 11). Pts received a median of 3 (1 – 11) prior therapies, 12 pts (57%) had prior SCT, and 4 pts received SAVE frontline. Maintenance post-SCT on SAVE was planned for 1 yr. At current SCT, 19% were in first complete remission (CR1 following SAVE), 81% were in CR2+ (SAVE or monotherapy). Median time to initiate post-SCT revumenib was 2.8 months (1.4 – 5.7) with median duration of therapy of 6.7 months (0.5 – 36). With a median follow-up of 18.2 months (95% CI 17.2 – 44.3), median overall survival (OS) and event-free survival (EFS) from SCT have not been reached; 1- and 2-year OS were 89%; 1- and 2-year EFS were 84% and 73%, respectively. The 1-year cumulative incidence of relapse (CIR) was 11% and death was 5%. In CR2+, 2-year OS was 93% and 1-year CIR was 13%. At last follow up, 29% remain on revumenib, and 71% have discontinued (relapse 14%, toxicity 14%, completion 14%, pt choice 14%, other illness 9%). The most common any grade adverse event (AE) was thrombocytopenia (86%; grade >3 43%), leading to dose modification in 48% and discontinuation in 10%. Graft-versus-host-disease occurred in 14% (grade >3 5%), however no other AE led to dose modification. Infections occurred in 14% (grade ≥3 10%); one pt discontinued due to grade 4 septic shock. No QTc prolongation was seen. In contrast, in a historical SCT cohort with the same genotypes treated prior to the advent of menin inhibitors (Table 1), pts transplanted at CR2+ had 2-year OS of 33% and 1-year CIR of 46%. Conclusions: Revumenib maintenance post-SCT was feasible in this heavily pretreated cohort. Thrombocytopenia was common often requiring dose modification, but no other significant toxicities were observed. Outcomes appear favorable compared to historical cohorts, supporting prospective evaluation of menin inhibition as maintenance. Clinical trial information: NCT04065399 , NCT05918913 . Rev vs. historical cohort. N 1-yr OS(%) 2-yr OS(%) 1-year CIR(%) Median F/U (mos) Rev 21 89 89 11 18.2 Rev CR2+ 17 93 93 13 33.3 Hist. 320 60 51 39 76 Hist. CR2+ 124 45 33 46 92