EHA: Oral combination shows high response rates in patients with hard-to-treat acute myeloid leukemia

MD Anderson Research News June 11, 2026

• Relapsed or refractory acute myeloid leukemia (AML) represents one of the most challenging hematologic cancers
• The menin inhibitor revumenib was approved by the FDA as a monotherapy in October 2025, but responses to monotherapy can be short-lived
• An all-oral revumenib-based combination therapy demonstrated a 71% composite complete remission rate in patients with hard-to-treat AML and specific genetic alterations

ABSTRACT: EHA-5060

STOCKHOLM, JUNE 11, 2026 — In patients with advanced acute myeloid leukemia (AML) harboring menin-dependent genetic alterations, 71% achieved a composite complete remission when treated with an all-oral combination therapy of revumenib, decitabine/cedazuridine and venetoclax, according to researchers at The University of Texas MD Anderson Cancer Center.

Results from the Phase 1/2 investigator-initiated SAVE clinical trial were published today in the Journal of Clinical Oncology and presented at the European Hematology Association (EHA) 2026 Congress. 

The trial enrolled adolescent and adult patients with relapsed or refractory AML with KMT2A rearrangements, NPM1 mutations or NUP98 rearrangements. The combination therapy achieved an 88% overall response rate and a complete remission or complete remission with partial hematologic recovery (CR/CRh) rate of 60%, with 80% of responding patients achieving measurable residual disease negativity by flow cytometry. The median duration of CR/CRh was 10.5 months overall, and the median had yet been reached among patients with KMT2A rearrangements, a signal of durable responses.

“These results highlight the potential of combining menin inhibition with BCL2 inhibition and a hypomethylating agent for genetically defined AML subtypes that historically have been very difficult to treat,” said principal investigator Ghayas Issa, M.D., associate professor of Leukemia. “Seeing durable remissions in patients who had already received multiple prior therapies is encouraging and supports continued evaluation of this combination strategy.”

The data was presented at EHA by Branko Cuglievan, M.D., associate professor of Leukemia and Pediatrics at UT MD Anderson. 

What is revumenib and how can it benefit patients with AML?

Menin plays a central role in driving leukemia in several AML subtypes. Revumenib is an oral menin inhibitor that blocks the interaction between menin and KMT2A, another key protein for leukemia growth, particularly in patients with AML harboring KMT2A rearrangements, NPM1 mutations or NUP98 rearrangements.

By blocking this interaction, revumenib disrupts leukemia growth signals. It was approved by the Food and Drug Administration for patients with KMT2A rearrangements or NPM1 mutations whose disease has relapsed or is no longer responding to standard treatments. However, responses to the treatment as a monotherapy can be short-lived, prompting researchers to investigate combination strategies.

Preclinical studies suggested that combining menin and BCL2 inhibition may enhance anti-leukemia activity, providing the rationale for combining revumenib with the BCL2 inhibitor venetoclax and the hypomethylating agent decitabine.

The SAVE trial enrolled 42 heavily pretreated patients ages 12 and older with the genetic subtypes, which are known to depend on the menin-KMT2A interaction for leukemia growth. Patients had received a median of two prior lines of therapy; approximately half had been treated previously with venetoclax, and one-third had a prior stem cell transplant.

How meaningful are these results for patients with relapsed or refractory AML?

Relapsed or refractory AML remains one of the most challenging hematologic malignancies to treat, especially in patients who have already received venetoclax-based regimens or multiple prior lines of therapy.

The promising results from this trial support further clinical development of the regimen, with planned randomized Phase 3 studies and investigations of the drug’s use in newly diagnosed patients with menin-dependent AML.

The most common severe side effects included fever associated with low white blood cell counts, lung infection and low platelets.

Researchers on the study also monitored treatment resistance, observing the emergence of new mutations affecting the menin-binding site in 13% of patients following treatment. While this is a substantially lower frequency than previously reported with revumenib monotherapy, these mutations were still associated with disease relapses, highlighting the continued need for next-generation menin inhibitors and additional rational combination strategies.

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This work was supported in part by Astex Pharmaceuticals, Taiho Oncology and Syndax Pharmaceuticals. A full list of collaborating authors and their disclosures can be found with the full paper in the Journal of Clinical Oncology.