Patients with a specific form of acute myeloid leukemia who experience a relapse have faced a sparse list of options. For those with NPM1 mutations, the most common genetic alteration in this disease, the US Food and Drug Administration approved the first targeted therapy in October 2025: Revumenib, developed by Syndax Pharmaceuticals. The mechanism is novel and early combination therapy data suggest potential beyond what the approved monotherapy shows.
What AML is and why NPM1 is the most common mutation
Acute myeloid leukemia is an aggressive blood cancer in which immature precursor cells grow uncontrollably and displace healthy blood cells. In Germany, around 4,000 people fall ill annually, mostly over age 60. Median survival after relapse is under one year for many patients.
NPM1 mutations, which affect the nucleophosmin protein, occur in up to 30 percent of all AML patients and represent the most common single gene mutation in the disease. The Menin protein plays a key role in these cases: it activates so-called HOX genes and keeps leukemia cells in an immature, division-active state. Revumenib blocks this interaction and is intended to force cancer cells to mature or undergo programmed cell death.
The FDA approved Revumenib (trade name Revuforj) on October 24, 2025, for adults and children from one year of age with relapsed or refractory NPM1-mutated AML. It was already the second approval for the drug: in November 2024, the agency had cleared Revumenib for leukemia patients with KMT2A rearrangements. Together, these two approvals potentially cover up to 40 percent of all AML patients, according to Syndax Pharmaceuticals.
What the study data show and where their limits lie
The basis for the new approval is the AUGMENT-101 study (Phase 1/2), in which 65 heavily pretreated patients with NPM1-mutated AML received Revumenib. According to OncLive and Syndax Pharmaceuticals, 23.1 percent achieved complete remission or remission with partial blood count recovery. The median remission duration was 4.5 months, and the median time to response was 2.8 months.
These numbers may sound modest, but they are not in context. For heavily pretreated patients after a relapse, there are few approved alternatives. Those who achieve remission have a real chance of long-term survival through subsequent stem cell transplantation. The European Society of Hematology has noted, however, that AUGMENT-101 as a single-arm study without a control group does not allow direct comparison with chemotherapy. Phase 3 data on Revumenib in randomized trials are still pending.
More promising are early data on combination therapies. In the SAVE study, researchers combined Revumenib with decitabine/cedazuridine and venetoclax. Interim analyses presented at ASH 2025 showed a 100 percent response rate in a small cohort with KMT2A rearrangements. However, randomized data from larger studies are still missing, but the principle of combining menin inhibition with BCL-2 inhibitors like venetoclax is considered conceptually sound in hematologic oncology.
Progress in blood cancer in historical perspective
Menin inhibitors fit into a series of genetically targeted therapies that have transformed hematologic oncology over two decades.
Imatinib, approved in 2001 for chronic myeloid leukemia, is considered the blueprint: the drug blocks the BCR-ABL1 fusion protein and raised the five-year survival rate for CML from under 30 to over 90 percent. For AML, development has been more challenging because the disease is genetically more heterogeneous. FLT3 inhibitors like midostaurin arrived in 2017, followed by IDH1 and IDH2 inhibitors in 2017 and 2018. Menin inhibitors now close another significant gap for a numerically important patient population.
Dr. Amir Fathi from Dana-Farber Cancer Institute, who was involved in Revumenib's development, called the approval a significant step for patients with a disease that has been difficult to treat. Further menin inhibitors are in clinical development: ziftomenib from Kura Oncology, bleximenib from Johnson & Johnson, and icovamenib. The ASH 2025 symposium devoted several sessions to menin inhibition, underscoring the growing clinical significance of the drug class.
When Revumenib will also be available in Europe
In Germany, Revumenib is currently available to affected patients within clinical trials or through individual compassionate use. Approval by the European Medicines Agency has not yet been granted, but corresponding application procedures are in preparation. The German Society for Hematology and Medical Oncology has not yet included Revumenib in its treatment recommendations and is waiting for data from randomized Phase 3 studies.
Ongoing combination therapy studies, including SAVE and others for first-line treatment, are expected to deliver initial results in 2026 and 2027. Whether Revumenib as a single agent or in combination is most beneficial, and at which treatment stage, remains one of the central open questions in AML research for the coming years.