Revumenib Maintenance After Allogeneic SCT Shows Feasibility in AML

Revumenib (Revuforj) used as maintenance therapy following allogeneic stem cell transplantation (ASCT) demonstrated feasibility and favorable survival outcomes in a heavily pretreated cohort of adult and pediatric patients with acute myeloid leukemia (AML), an analysis presented at the 2026 ASCO Annual Meeting found.¹

In 24 patients with NPM1-mutated (NPM1m), KMT2A-rearranged (KMT2Ar), or NUP98-rearranged (NUP98r) AML who received revumenib as post-ASCT maintenance, median overall survival (OS) and event-free survival (EFS) from the time of transplant had not been reached at a median follow-up of 18.2 months (95% CI, 17.2-44.3). The 1- and 2-year OS rates were both 90%; 1- and 2-year EFS rates were 82% and 72%, respectively. The 1- and 2-year cumulative incidence of relapse (CIR) was 13% and 24%, respectively; the 1- and 2-year nonrelapse mortality rates were 4%.

These outcomes compared favorably to a historical ASCT cohort with the same genotypes treated prior to the availability of menin inhibitors. In a landmark analysis that excluded patients who relapsed or died before 82 days, the median time to initiation of posttransplant revumenib in the study cohort, the 1-year CIR in the historical cohort was 12% for patients transplanted in first complete remission (CR1) and 40% for those transplanted in second complete remission (CR2) or beyond. By contrast, patients in the revumenib maintenance cohort had a 1-year CIR of 0% in CR1 and 17% in CR2 or beyond.

“Despite the heavily pretreated nature of this cohort, survival outcomes appear encouraging relative to historical expectations,” said Hannah Goulart, MD, of The University of Texas MD Anderson Cancer Center, during the oral presentation of data.¹ “These findings support further prospective evaluation of menin inhibition as posttransplant maintenance therapy.”

Study Background and Patient Population

Relapse after ASCT remains a significant challenge in AML. Revumenib, a menin inhibitor, is currently FDA approved for the treatment of relapsed/refractory NPM1m or KMT2Ar acute leukemia, but its safety and efficacy profile in the posttransplant maintenance setting had not been characterized prior to this analysis.

The cohort included 13 adult and 11 pediatric patients, with a median age of 22 years (range, 1-74). KMT2Ar disease represented the majority of cases (71%), while 25% of patients had NPM1m AML, seen exclusively in adults. One pediatric patient had NUP98r AML. Patients were heavily pretreated, having received a median of 3 prior therapies, and more than half had undergone a prior ASCT, including 1 patient with 2 prior transplants.

Before proceeding to ASCT, patients received revumenib as monotherapy through the AUGMENT-101 trial (NCT04065399) or an expanded access program (NCT05918913), or in combination with oral decitabine and venetoclax (Venclexta) through the SAVE trial (NCT05360160). Most patients received pretransplant combination therapy with the SAVE regimen, though a greater proportion of pediatric patients received revumenib as a single agent pretransplant.

Matched unrelated donor transplant was the most common donor source overall; however, the pediatric cohort demonstrated greater heterogeneity, with cord blood transplantation representing the most common donor type in that subgroup. Most patients received myeloablative conditioning regimens, though the majority of adults received reduced-intensity regimens. Nearly 90% of patients received tacrolimus as graft-vs-host disease (GVHD) prophylaxis, which was continued during posttransplant revumenib maintenance, and more than half received posttransplant cyclophosphamide.

The median time to initiating revumenib post-ASCT was 82 days, with most patients having fully recovered blood counts at the time of initiation. The median duration of post-transplant revumenib maintenance was just over 10 months, though several patients remained on therapy substantially longer, including some for up to 3 years. At the time of data cutoff, 7 patients were actively receiving maintenance therapy.

MRD Outcomes

Almost 80% of patients were in a measurable residual disease (MRD)-negative remission by flow cytometry pretransplant, increasing to 88% posttransplant. Among NPM1m patients, 2 of 5 were MRD negative by next-generation sequencing (NGS)-based assay with a sensitivity of 5 × 10⁻⁵ prior to initiating posttransplant maintenance; following initiation, 2 additional patients became NPM1 MRD negative by NGS.

Safety Profile: Thrombocytopenia Predominates

The most common treatment-emergent adverse event (AE) was thrombocytopenia, occurring in 83% of patients, with grade 3 or higher events in 46%. Dose interruptions or reductions were used to manage thrombocytopenia in the majority of affected patients, and most were able to resume therapy; however, 3 patients (13%) discontinued revumenib due to persistent thrombocytopenia.

Neutropenia was the next most common treatment-emergent AE, occurring in 21% of patients, with 1 patient discontinuing as a result. Infections were reported in 4 patients; 1 patient discontinued treatment during an episode of septic shock. Nausea was uncommon and generally low grade, though 1 patient required dose modifications, ultimately resuming maintenance therapy. Notably, no QTc prolongation or differentiation syndrome was observed during posttransplant maintenance with revumenib.

Clinical Implications

Investigators concluded that revumenib maintenance was feasible in this heavily pretreated population, with thrombocytopenia representing the primary management challenge. As such, the findings add to the growing body of evidence for menin inhibitors in genetically defined AML subtypes and raise the question of how best to integrate revumenib into the posttransplant setting.

However, the retrospective, single-institution design and small sample size limit the generalizability of these data. Prospective, randomized studies will be needed to confirm the benefit of revumenib maintenance and to better define the optimal patient population, dosing strategy, and duration of therapy.

DISCLOSURES: Goulart did not have any relationships to disclose.

REFERENCES

1. Goulart H, Okeleji O, DiNardo CD, et al. . Revumenib as maintenance for AML following allogeneic stem cell transplantation. J Clin Oncol. 2026;44(suppl 16):6505. doi:10.1200/JCO.2026.44.16_suppl.6505