Background: Acute myeloid leukemia (AML) is a rapid-progressing malignancy characterized by the proliferation of immature myeloid cells, leading to bone marrow dysfunction. Acute myeloid leukemia (AML) is a rapid-progressing malignancy characterized by the proliferation of immature myeloid cells, leading to bone marrow dysfunction. Acute myeloid leukemia (AML) with KMT2A rearrangements or NPM1 mutations represents a subset of leukemia with poor prognosis and limited treatment options. Revumenib, a selective Menin inhibitor, has emerged as a potential therapeutic agent targeting these genetic alterations. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Revumenib in treating AML with KMT2A rearrangements or NPM1 mutations in adult patients.

Methods: This systematic review follows PRISMA guidelines, focusing on studies evaluating Revumenib (SNDX-5613) in adult AML patients with KMT2A rearrangements or NPM1 mutations. A comprehensive literature search was conducted across multiple databases, including PubMed and clinical trial registries, up to July 2024. Two studies were identified and included in the analysis. The studies' primary outcomes were overall response rate (ORR), complete remission (CR), and treatment-related adverse events (TRAEs). Data were extracted and synthesized, and a meta-analysis was performed using a random-effects model to pool the results. The quality assessment used the Newcastle-Ottawa Scale (NOS).

Results: Two studies met the inclusion criteria. The pooled analysis demonstrated a high Overall Response Rate (ORR) of 42% (95% CI: 34-51%) for Revumenib, with a complete remission (CR) rate of 26% (95% CI: 19-34%). The median duration of CR was 6.4 months. Notably, 69% of patients who achieved CR also reached measurable residual disease (MRD) negativity, indicating deep molecular responses. The most common Treatment-related adverse events (TRAEs) ) occurred in 80.5% of patients (95% CI, 73.1% to 87.9%), with severe TRAEs in 25.9% (95% CI, 17.7% to 34.1%). Despite high TRAE incidence, only 6.4% discontinued therapy due to adverse effects. TRAEs were nausea (39%), differentiation syndrome (21%), and QTc prolongation (19%). Grade ≥3 TRAEs occurred in 48% of patients, with the most frequent being febrile neutropenia (28%), differentiation syndrome (13%), and QTc prolongation (12%). No treatment-related deaths were reported.

Discussion: Revumenib demonstrates promising efficacy in achieving high response rates and MRD negativity in adult patients with relapsed or refractory AML with KMT2A rearrangements or NPM1 mutations. However, the treatment is associated with significant adverse events, emphasizing the need for careful monitoring and management. The safety profile is manageable with appropriate monitoring. The high ORR and depth of remission highlight Revumenib's potential as a therapeutic option in a challenging patient population. The limited number of studies and the small sample size underscore the necessity for ongoing clinical trials further to establish the therapeutic potential and long-term safety of Revumenib. These findings highlight Revumenib as a potential new standard of care for this challenging subset of AML, pending further validation from larger, more comprehensive studies. Revumenib offers promising outcomes for relapsed/refractory AML patients with KMT2A rearrangements or NPM1 mutations, supporting its integration into clinical practice.

Disclosures

No relevant conflicts of interest to declare.

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2024
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