This article reviews recent pivotal trials in AML and CLL, highlighting advances in MRD-guided therapy, targeted agents, and chemotherapy-sparing approaches. GIMEMA studies demonstrate the value of personalized treatment based on genetic risk and disease biology, optimizing remission depth while minimizing toxicity. The AUGMENT-101 trial underscores precision medicine in relapsed/refractory acute leukemia, using Revumenib to target KMT2A-rearranged or NPM1-mutated disease. Together, these studies emphasize translational relevance, supporting clinicians in integrating biology-driven, individualized strategies to improve patient outcomes.
The GIMEMA Trials1-5
Overview
- Recent GIMEMA trials in Acute Myeloid Leukemia (AML) and CLL focus on improving frontline therapy through minimal residual disease (MRD) guided treatment decisions, intensified induction strategies, and chemotherapy-free regimens. Together, these trials explore personalized and targeted approaches aimed at increasing remission depth while minimizing toxicity.
Signficance
- GIMEMA AML1310 demonstrated that tailoring post-remission therapy based on genetic risk and MRD status can optimize outcomes while limiting unnecessary allogenic transplant exposure. AML1718 demonstrated that adding venetoclax to intensive induction may deepen responses in intermediate- and high-risk AML. In CLL, trials such as LLC1114 and the VeRitAs study examined targeted combinations (ibrutinib-rituximab and fixed-duration venetoclax-rituximab) to offer effective, chemo-free options for both older “unfit” patients and those with adverse biology.
- The full list of GIMEMA clinical studies can be viewed here
Clinical Implications
- These trials highlight a shift toward individualized leukemia care using biology, MRD, and targeted agents to replace one-size-fits-all chemotherapy strategies. If integrated into practice, these approaches could reduce treatment-related morbidity, increase durability of remission, and expand non-chemotherapy options across AML, CLL, and other leukemias.
AUGMENT-101 Trial (NCT04065399)6
Overview
- Phase 1/2, open-label study of Revumenib (SNDX-5613), an oral small-molecule inhibitor of the menin-KMT2A interaction, in patients with R/R acute leukemia. It enrolls patients with leukemias harboring either a KMT2A rearrangement (KMT2Ar) or NPM1 mutation.
Significance
- KMT2Ar and NPM-1 mutated acute leukemias represent high-risk molecular subtypes with historically poor prognosis and limited targeted-therapy options. This study offers a molecular-based, rational therapy aimed at a genetic driver rather than a broadly cytotoxic chemotherapy.
Clinical Implications
- This study underscores the feasibility and benefits of precision medicine using genetic/molecular markers (KMT2A rearrangement or NPM1 mutation) to guide therapy in R/R acute leukemia. The data support Revumenib as a new non-cytotoxic, mutation-targeted option that can potentially improve outcomes while expanding therapeutic choices beyond conventional chemo.
Sources:
- Gimema.it, 2024, www.gimema.it/en/. Accessed 3 Dec. 2025.
- “Risk-Adapted, MRD-Directed Therapy for Young Adults with Newly Diagnosed Acute Myeloid Leukemia (AML1310).” Clinicaltrials.gov, 6 Aug. 2018, clinicaltrials.gov/study/NCT01452646. Accessed 3 Dec. 2025.
- “Venetoclax Add in Combination with Fludarabine, Cytarabine and Idarubicin in Induction for Acute Myeloid Leukemia (V-FIRST).” Clinicaltrials.gov, 10 Apr. 2024, clinicaltrials.gov/study/NCT03455504. Accessed 3 Dec. 2025.
- “Outcomes of Unfit Patients with CLL Included in the GIMEMA LLC1114 Trial Who Discontinued Ibrutinib due to Reasons Other than Disease Progression.” Clinicaltrials.gov, 10 Apr. 2024, clinicaltrials.gov/study/NCT06084923. Accessed 3 Dec. 2025.
- “Activity and Safety of Front-Line Venetoclax and Rituximab in Young and Fit Patients with Chronic Lymphocytic Leukemia (VeRitAs).” Clinicaltrials.gov, 24 Nov. 2023, clinicaltrials.gov/study/NCT03455517. Accessed 3 Dec. 2025.
- “A Study of Revumenib in R/R Leukemias Including Those with an MLL/KMT2A Gene Rearrangement or NPM1 Mutation (AUGMENT-101).” Clinicaltrials.gov, 7 Nov. 2025, clinicaltrials.gov/study/NCT04065399. Accessed 3 Dec. 2025.
