Menin Inhibitors in AML: Frequently Asked Questions

Menin inhibitors are one of the most significant advances in acute myeloid leukemia (AML) in recent years. With 2 agents now FDA approved and more in the pipeline, oncology pharmacists need a working fluency with this drug class. Here are answers to the questions asked most often at the bedside.

What Is a Menin Inhibitor, and Why Does It Matter in AML?

AML is diagnosed in approximately 22,720 individuals annually—12,160 males and 10,560 females—with the vast majority of cases occurring in adults. The disease accounts for approximately 1 in 3 leukemias in adults and approximately 1% of all cancers overall. An estimated 11,500 individuals will die from AML each year, underscoring the continued need for effective therapeutic options in a disease with historically poor outcomes.¹

Underlying that poor prognosis is a disease defined by molecular heterogeneity. Under normal physiology, the MEN1 protein functions as a tumor suppressor, but in certain AML subtypes, it takes on an oncogenic role, forming a complex with the KMT2A gene product that drives aberrant gene expression and fuels leukemic cell proliferation. Menin inhibitors block this protein-protein interaction, disrupting a fundamental driver of disease in patients whose tumors carry either an NPM1 mutation or a KMT2A rearrangement.² These 2 molecular subgroups represent approximately 40% of AML cases, making menin inhibition broadly relevant.³

As monotherapy, menin inhibitors have demonstrated overall response rates ranging from approximately 40% to 60%, with complete remission (CR) or CR with partial hematologic recovery achieved in roughly 25% to 45% of patients.²

Which Agents Are FDA Approved?

As of June 2026, revumenib (Revuforj; Syndax Pharmaceuticals) and ziftomenib (Komzifti; Kura Oncology) are the only FDA-approved menin inhibitors for AML. Revumenib received approval in October 2025 for adult and pediatric patients 1 year and older with relapsed or refractory (R/R) AML harboring a susceptible NPM1 mutation. This followed its earlier 2024 approval for KMT2A-rearranged acute leukemia, making revumenib the first and only FDA-approved therapy for both R/R AML with an NPM1 mutation and R/R acute leukemia with a KMT2A translocation.⁴

In the open-label, multicenter AUGMENT-101 trial (NCT04065399), revumenib produced a CR rate with a partial hematological recovery (CRh; CR + CRh) rate of 23.1% (95% CI, 13.5%-35.2%) in patients with R/R NPM1-mutated AML, with a median response duration of 4.5 months (95% CI, 1.2-8.1). Primary efficacy outcome measures included CR rate, CRh rate, CR + CRh duration, and conversion from transfusion dependence to transfusion independence. Among patients who were transfusion-dependent at baseline, 17% achieved transfusion independence during the postbaseline period.⁴

Ziftomenib was approved in November 2025 for adults with R/R AML harboring a susceptible NPM1 mutation who have no suitable alternative treatment options. The decision was supported by data from the open-label, single-arm KO-MEN-001 trial (NCT04067336), in which ziftomenib was evaluated in 112 adults with R/R NPM1-mutant AML. The CR + CRh rate was 21.4% (95% CI, 14.2%-30.2%) with a median duration of 5 months (95% CI, 1.9-8.1). Among transfusion-dependent patients at baseline, 21.2% achieved transfusion independence during the postbaseline period.⁵

What Are the Key Toxicities to Monitor?

Pharmacists must monitor for 3 toxicities with this class:

Differentiation syndrome is the most serious concern and a class effect. It can develop promptly and result in poor outcomes; management strategies include monitoring for inflammatory response and holding the menin inhibitor while administering steroids to control the inflammatory cascade. Before initiating therapy, pharmacists should ensure the care team has a documented differentiation syndrome protocol in place—one that outlines early recognition, prompt initiation of high-dose corticosteroids such as dexamethasone, and temporary discontinuation of the targeted agent in severe cases.^2,6

QTc prolongation requires baseline and ongoing ECG monitoring. This risk is amplified in patients receiving concurrent QT-prolonging medications such as antiemetics or antibiotics, both of which are common in the AML inpatient setting. Notably, ziftomenib does not appear to cause QTc prolongation and has shown no appreciable CYP3A4 inhibitory effect, which may inform agent selection for patients with high baseline cardiac risk or those receiving complex regimens.^7,8

Drug-drug interactions, particularly with azole antifungals, are critical for pharmacists to be alert for. Careful monitoring throughout treatment and potential dose adjustments are required, given how commonly antifungals are coadministered in AML.⁷

Where Does this Class Fit in the Treatment Landscape?

The approvals to date cover the R/R setting, but the trajectory is toward earlier use. Combination therapies with azacitidine and venetoclax or intensive chemotherapy have achieved high response rates in newly diagnosed patients, suggesting menin inhibitors could work as initial treatment. Clinical trials are actively exploring frontline combinations, maintenance post transplant, and use at molecular relapse, making ongoing familiarity with this class essential for pharmacists who will encounter it at multiple points in the patient journey.⁹

REFERENCES

1. Key statistics for acute myeloid leukemia (AML). American Cancer Society. Updated January 13, 2026. Accessed June 25, 2026. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/key-statistics.html

2. Cumming S. Menin inhibitors in AML: Bridging the gap between trial data and clinical practice. AML Hub. October 8, 2025. Accessed June 25, 2026. https://aml-hub.com/medical-information/menin-inhibitors-in-aml-bridging-the-gap-between-trial-data-and-clinical-practice

3. FDA approves menin inhibitor for patients with acute leukemia with NPM1 mutation, backed by Dana-Farber science. News release. Dana-Farber Cancer Institute. November 4, 2025. Accessed June 25, 2026. https://www.dana-farber.org/newsroom/news-releases/2025/fda-approves-menin-inhibitor-for-patients-with-acute-leukemia-with-npm1-mutation-backed-by-dana-farber-science

4. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. FDA. October 24, 2025. Accessed June 25, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation

5. FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with an NPM1 mutation. FDA. Updated November 13, 2025. Accessed June 25, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ziftomenib-relapsed-or-refractory-acute-myeloid-leukemia-npm1-mutation

6. Mirabile M, Ursu S, Fazal S. Managing differentiation syndrome associated with treatment for AML: symptom management overview, leukemia, adverse events. J Hematol Oncol Pharm. 2024;14(1). Accessed June 25, 2026. https://www.jhoponline.com/issue-archive/2024-issues/february-2024-vol-14-no-1/managing-differentiation-syndrome-associated-with-treatment-for-aml

7. Cumming S. Managing side effects of menin inhibitors in clinical practice. AML Hub. April 28, 2026. Accessed June 25, 2026. https://aml-hub.com/medical-information/managing-side-effects-of-menin-inhibitors-in-clinical-practice

8. Helwick C. Novel menin inhibitors show safety and activity in several clinical trials. ASCO Post. February 25, 2025. Accessed June 25, 2026. https://ascopost.com/issues/february-25-2025/novel-menin-inhibitors-show-safety-and-activity-in-several-clinical-trials/

9. Alati C, Molica M, Pitea M, et al. Menin inhibition in acute myeloid MLL rearranged leukemias: a new target for precision care. Cancers (Basel). 2026;18(4):637. doi:10.3390/cancers18040637