Early Data Show Revumenib Offers Maintenance Option in AML Following SCT

Allogeneic stem cell transplantation (SCT) is a potentially curative strategy for patients with acute myeloid leukemia (AML), but relapse remains common. With revumenib (Revuforj; Syndax) approved for patients with relapsed/refractory NPM1-mutated (NPM1mt) or KMT2A-rearranged (KMT2Ar) acute leukemia, the next question is this: Could this menin inhibitor offer a safe, effective post-SCT maintenance option? Data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting examined this question.¹

Hannah Goulart, MD, a hematology/oncology fellow at the University of Texas MD Anderson Cancer Center in Houston, presented data from 21 patients, including 11 adults and 10 pediatric patients. According to the abstract, those with NPM1mt, KMT2Ar, or NUP98-rearranged (NUP98r) AML could continue post-SCT revumenib maintenance following revumenib given prior to transplant, either as monotherapy (per AUGMENT-101, NCT04065399), in combination on a clinical trial (per SAVE, NCT05360160), or through expanded access (NCT05918913). Revumenib was restarted at the dose given prior to SCT with adjustment for azoles.¹

Results. The median follow-up was 18.2 months (95% CI, 17.2-44.3), with median overall survival (OS) and event-free survival (EFS) from SCT not reached. Investigators reported that the 1- and 2-year OS were 89%; 1- and 2-year EFS rates were 84% and 73%, respectively. The 1-year cumulative incidence of relapse (CIR) was 11%, and death was 5%. For patients at second complete remission or beyond, the 2-year OS was 93% and 1-year CIR was 13%. At last follow-up, 29% of patients remain on revumenib and 71% have stopped therapy, with 14% ending therapy due to relapse, 14% due to toxicity, 14% completing therapy, 14% due to patient choice, and 9% due to other illnesses.

Adverse events. The most common adverse event (AE) of any grade was thrombocytopenia (86%; grade 3 or higher in 43%), leading to dose modifications in 48% of patients and discontinuation for 10%. Graft-vs-host-disease occurred in 14% (grade 3 or higher in 5%); however, no other AE prompted dose modification. Infections occurred in 14%, with 10% grade 3 or higher; 1 patient stopped therapy following grade 4 septic shock. No QTc prolongation was seen. These results compared favorably with an historical SCT cohort with the same genotypes treated prior to the arrival of menin inhibitors; in that group, patients transplanted at the second remission or later had a 2-year OS of 33% and a 1-year CIR of 46%.¹

Following a request from The American Journal of Managed Care® (AJMC®), Nick Botwood, MBBS, Syndax Pharmaceuticals’ head of research and development and chief medical officer, answered several questions via email.

AJMC: Discuss the unmet need in the population studied, especially the pediatric patients.

Botwood: This study was looking at a cohort of heavily pretreated patients with KMT2Ar, NPM1m, or NUP98r AML who received the menin inhibitor revumenib before and after an allogeneic [SCT]. Unfortunately, posttransplant relapse and poor outcomes remain common in this patient population. This study reported a historical 2-year OS rate of 33% and 1-year cumulative relapse rate of 40% among patients with these genotypes who underwent a transplant in second complete remission or beyond prior to the advent of menin inhibitors.

There is a critical need for therapies that can reduce the risk of relapse post transplant among patients with KMT2Ar, NPM1m, or NUP98r acute leukemias, especially among children. For instance, KMT2A rearrangements occur in approximately 80% of infants with [acute lymphocytic leukemia] and 35% to 60% of infants with AML and are associated with early treatment failure and poor outcomes.

AJMC: Describe why revumenib’s mechanism may be applicable in the posttransplant maintenance setting.

Botwood: Revumenib is a first-in-class small molecule that inhibits the menin-KMT2A interaction, thereby blocking key drivers of leukemogenesis in patients with certain genetic subtypes of acute leukemia.

Revumenib is currently approved in relapsed or refractory NPM1-mutated AML or KMT2A-translocated acute leukemia. The safety and efficacy of revumenib in the posttransplant setting is an area of active research. In addition to suppressing leukemogenesis, emerging preclinical data suggest that menin inhibition may also have immunomodulatory properties that could enhance the graft-vs-leukemia effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient. These observations provide the biological rationale for evaluating revumenib as maintenance therapy following [SCT].

AJMC: What challenges do patients with acute leukemia/AML typically encounter post transplant that revumenib may help address?

Botwood: There is strong clinical interest in studying revumenib as posttransplant maintenance to understand if it can reduce the risk of relapse and improve long-term outcomes for patients with certain types of acute leukemia. The outcomes observed in the study recently presented at ASCO appear very encouraging relative to historical benchmarks. Among patients with KMT2A, NPM1, or NUP98 alterations who were transplanted in second complete remission or beyond and resumed revumenib post transplant, the 1-year cumulative relapse rate was 17%, as compared to 40% in a similar historical cohort. These data support further clinical research and prospective evaluation of revumenib in this setting.

AJMC: Can revumenib be taken alongside other therapies for other conditions?

Botwood: Revumenib may be taken with many commonly prescribed medicines, including gastric acid–reducing agents such as proton pump inhibitors, a differentiating aspect of its [pharmacokinetic] profile. Physicians are advised to avoid use with strong or moderate CYP3A4 inducers.

AJMC: What does the safety profile look like for revumenib in this setting?

Botwood: The safety observed in the posttransplant setting was consistent with the established safety profile for revumenib. Thrombocytopenia was the most common adverse event observed in this study.

AJMC: Discuss the goals, design, and anticipated time frames for the MenTain study.

Botwood: The MenTain study is one of several planned or ongoing trials evaluating revumenib as posttransplant maintenance for patients with KMT2Ar, NPM1m, or NUP98r acute leukemias. MenTain will be the first randomized, placebo-controlled trial specifically focused on evaluating revumenib in this setting. The primary end point will be relapse-free survival. This is an important trial that will allow us to further elucidate the therapeutic potential of revumenib.

Reference

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