Revumenib Shows Efficacy in Patients With AML and Genetic Alterations

Revumenib shows promise for high-risk patients with AML with specific genetic mutations, demonstrating efficacy with no new safety signals.

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Patients with KMT2A rearrangements and NPM1 mutations have high risk and face unfavorable prognosis, but menin inhibitors are a new class of targeted agents with the potential to treat these subtypes. Revumenib (Revuforj; Syndax Pharmaceuticals) has shown clinically meaningful responses in heavily pretreated populations with relapsed or refractory acute myeloid leukemia (R/R AML) with NPM1 mutation NPM1m, KMT2A rearrangement (KMT2Ar), and NUP98 rearrangement (NUP98r), according to data in posters presented at the European Hematology Association Congress (EHA).^1-3

Revumenib was approved in November 2024 by the FDA to treat R/R acute leukemia with KMT2A translocation and is currently under review with the FDA to treat R/R mutant NPM1 AML.^4,5 There are currently no targeted therapies approved to treat R/R mutant NPM1 AML.

“Revumenib has shown a potential best-in-class efficacy profile, and the latest data in R/R mNPM1 AML underscore the opportunity for revumenib to become a standard-of-care treatment for this patient population in addition to R/R KMT2Ar acute leukemia,” said Ibrahim Aldoss, MD, associate professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, in a statement.⁶ “The revumenib data in R/R mNPM1 AML presented at EHA are impressive, with 26% of patients achieving [complete remission/complete remission with partial hematologic recovery] and nearly 50% achieving an overall response with a medicine that was generally well tolerated. Furthermore, the 23-month median overall survival observed in responders in a subgroup analysis is very encouraging.”

Updated results from the phase 2 AUGMENT-101 study (NCT04065399) on revumenib to treat NPM1–mutated AML in 77 patients found a complete response (CR) plus complete response with partial hematology recovery (CRh) of 26%.¹ The rates were similar across subgroups, and the median time to first CR/CRh was 2.8 months with a median duration of CR/CRh of 4.7 months. Plus, the overall response rate was 48.1%. The patients included in this study were older, with 49.4% over age 65, and more than a third (35%) had received ≥ 3 prior lines of therapy.

In the updated results of the same trial studying revumenib in patients with KMT2Ar acute leukemia, 116 patients had received at least 1 dose of the therapy, and 97 patients had sufficient follow-up to be evaluated for the efficacy of the treatment at the time of the data cutoff.² The rate of CR + CRh was 22.7%, with the median duration of response for these patients being 6.4 months. The time to first CR + CRh was 2.0 months, and the median duration of that response was 6.4 months.

In addition, a third (34%) went on to receive hematopoietic stem cell transplantation (HSCT). Of the patients who achieved CR + CRh, 61.1% achieved negative minimal residual disease (MRD) status.

“The new data from AUGMENT-101 continue to highlight Revuforj’s best-in-class profile and its potential to transform the treatment paradigm for acute leukemia patients with certain genetic alterations,” Nick Botwood, MBBS, head of research & development and chief medical officer at Syndax, said in a statement. “The compelling AUGMENT-101 results led to the FDA approval of Revuforj for R/R acute leukemia with a KMT2A translocation and serve as the foundation for the supplemental NDA [new drug application] we submitted to the FDA for R/R mNPM1 AML, another area of high unmet need.”

Finally, in the AUGMENT-101 phase 1 study, 5 patients with NUP98r AML were treated with revumenib at a variety of dosages: 113 mg every 12 hours, 163 mg every 12 hours, and 163 mg 3 times a day. There were responses for the doses of 113 mg and 163 mg every 12 hours. Three of the patients achieved a morphological remission and 1 patient attained MRD negativity and then went on to receive HSCT.

For all the studies, there were no new safety signals.

References

1. Arellano ML, Thurman MJ, DiPersio JF. Et al. Revumenib for patients with relapsed or refractory (R/R) nucleophosmin 1–mutated (NPM1m) acute myeloid leukemia (AML): updated results from the phase 2 AUGMENT-101 study. Presented at: EHA 2025 Congress; June 12-15, 2025; Milan, Italy. Poster PS1467.

2. Aldoss I, Issa GC, Blachly JS, et al. Updated results and longer follow-up from the AUGMENT-101 phase 2 study of revumenib in patients with relapsed or refractory (R/R) KMT2Ar acute leukemia. Presented at: EHA 2025 Congress; June 12-15, 2025; Milan, Italy. Poster PS1473.

3. Issa GC, Cuglievan B, DiPersio JF, et al. Revumenib activity in patients with NUP98r acute myeloid leukemia: results from the AUGMENT-101 phase 1 study. Presented at: EHA 2025 Congress; June 12-15, 2025; Milan, Italy. Poster PS1501.

4. Rosa K. FDA approves revumenib for R/R acute leukemia with a KMT2A translocation. OncLive^®. November 15, 2024. Accessed June 12, 2025. https://www.onclive.com/view/fda-approves-revumenib-for-r-r-acute-leukemia-with-a-kmt2a-translocation

5. Syndax announces publication of pivotal revumenib data in relapsed or refractory mNPM1 acute myeloid leukemia in the journal Blood. News release. Syndax Pharmaceuticals. May 7, 2025. Accessed June 12, 2025. https://ir.syndax.com/news-releases/news-release-details/syndax-announces-publication-pivotal-revumenib-data-relapsed-or

6. Syndax presents new Revuforj (revumenib) data in relapsed/refractory mNPM1 and NUP98r acute leukemia from AUGMENT-101 trial at EHA 2025. News release. Syndax Pharmaceuticals. June 12, 2025. Accessed June 12, 2025. https://ir.syndax.com/news-releases/news-release-details/syndax-presents-new-revuforjr-revumenib-data-relapsedrefractory