Oral Revumenib Maintenance After Salvage Therapy for Extramedullary NPM1-Mutated Acute Myeloid Leukemia Relapse

Introduction/Background/Significance: Extramedullary relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation is an uncommon but clinically challenging manifestation of post-transplant relapse. Revumenib is approved for relapsed/refractory NPM1-mutated AML, but data remain limited regarding responses in extramedullary disease and its use as a lower-burden, maintenance-like strategy after salvage therapy. We describe a patient with relapsed post-transplant NPM1-mutated AML involving nasal leukemia cutis, multifocal osseous disease, and marrow measurable residual disease (MRD), who achieved remission after revumenib-containing salvage therapy and remained in remission on oral revumenib monotherapy.

Materials and Methods/Case Presentation/Objective: A 71-year-old man was diagnosed with core-binding factor AML with t(8;21) in 2017 and treated with 7+3 induction followed by intermediate-dose cytarabine consolidation. He relapsed in 2018 with NPM1 mutated AML and underwent re-induction with clofarabine/cytarabine followed by haploidentical allogeneic transplantation. He relapsed again in 2019 and was treated with decitabine/venetoclax followed by two donor lymphocyte infusions, achieving remission. In June 2025, he developed an enlarging nasal papule and gum hyperplasia. Nasal biopsy demonstrated leukemia cutis with tumor cells positive for CD43, CD117, BCL2, and myeloperoxidase. Peripheral blood testing showed NPM1 positivity with variant allele frequency of 7.2%. Bone marrow biopsy showed normocellular marrow without morphologic AML but MRD by flow cytometry at 0.45% and NPM1 positivity at 27%. PET/CT demonstrated FDG-avid disease involving the right nasal tip and numerous osseous lesions. Molecular testing of nasal tissue identified NPM1, IDH2, EZH2, and NRAS alterations.

Results/Description/Main Outcome Measure(s): He started salvage chemotherapy with cladribine, low dose cytarabine, venetoclax, and revumenib in September 2025, and received five fractions of radiation to the nasal lesion. Post-cycle 1 marrow showed no morphologic AML, MRD negativity by flow, and negative NPM1, IDH1, and IDH2 PCR. PET/CT in October 2025 showed complete resolution of nasal and osseous FDG uptake. Given his preference to avoid further parenteral therapy, he subsequently received an oral regimen of venetoclax and continuous revumenib beginning November 2025. Venetoclax was discontinued after 7 days because of gastrointestinal toxicity, fatigue, and dysgeusia, and he continued revumenib 160 mg twice daily as monotherapy. As of April 2026, he remained in complete remission with hematologic recovery and persistently negative NPM1 and IDH2 PCR.

Conclusion(s).: This case illustrates durable multi-compartment remission in a relapsed, post-transplant NPM1-mutated AML with cutaneous and osseous extramedullary disease after revumenib-containing salvage therapy. Although revumenib is approved for relapsed/refractory NPM1-mutated AML, limited data describe extramedullary responses and subsequent maintenance-like use. Durable remission on single-agent oral revumenib after discontinuation of parenteral chemotherapy and venetoclax supports further study of menin inhibition as a lower-burden maintenance strategy after salvage therapy.

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References: Arellano ML, Thirman MJ, DiPersio JF, et al. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood. 2025;146(9):1065-1077. doi:10.1182/blood.2025028357