Abstract
Acute myeloid leukemia (AML) treatment relied on anthracyclines and cytarabine based intensive chemotherapy. However, clinical outcomes are unsatisfied for patients with intermediate/adverse cytogenetics based on European Leukemia Net (ELN) risk stratification 2022 (ELN 2022), and relapses also remain common even in patients with favorable-risk cytogenetics with measurable residual disease (MRD). There is an urgent unmet need for optimizing intensive chemotherapy regimens with novel agents, to enhance the MRD-negative rate, achieve durable remission, and improve the prognosis of AML. Preliminary results showed that adding a B-cell lymphoma-2 (BCL-2) inhibitor to intensive chemotherapy could improve treatment efficacy. Sonrotoclax is a potent, selective, next-generation BCL-2 inhibitor that effectively inhibits both the wide-type BCL-2 and several BCL-2 mutants. We hypothesize that the addition of sonrotoclax to intensive chemotherapy may enhance the treatment efficacy for AML without untoward toxicity. Here, we describe the rationale and design of a single-arm, multicenter, phase 2 study evaluating the efficacy and safety of sonrotoclax combined with chemotherapy as an induction therapy in newly diagnosed patients with AML who are fit for intensive chemotherapy, followed by stratified subsequent consolidation and maintenance treatment based on patients' ELN2022 at diagnosis and MRD results after induction.: NCT06497062.
Overview
- The study aims to evaluate the efficacy and safety of adding the BCL-2 inhibitor sonrotoclax to intensive chemotherapy as an induction therapy for newly diagnosed patients with acute myeloid leukemia (AML) who are fit for intensive chemotherapy.
- The study will investigate the potential of sonrotoclax to enhance treatment efficacy for AML without untoward toxicity, specifically in patients with intermediate/adverse cytogenetics based on the European Leukemia Net (ELN) risk stratification 2022 (ELN 2022)
- The study will enroll newly diagnosed patients with AML who are fit for intensive chemotherapy and will evaluate the outcome of sonrotoclax combined with chemotherapy as an induction therapy, followed by subsequent consolidation and maintenance treatment based on patients' ELN2022 at diagnosis and MRD results after induction
Comparative Analysis & Findings
- This study aims to compare the treatment outcomes of patients with AML who receive sonrotoclax combined with chemotherapy to those who receive chemotherapy alone
- The study will evaluate the rate of MRD negativity after induction therapy, as well as overall survival and event-free survival rates, to determine the potential benefits of adding sonrotoclax to chemotherapy
- Preliminary results have shown that adding a BCL-2 inhibitor to intensive chemotherapy can improve treatment efficacy, providing a promising direction for the study
Implications and Future Directions
- The study's findings could have significant implications for the treatment of AML, particularly for patients with intermediate/adverse cytogenetics, and may lead to improved treatment outcomes and increased MRD negativity rates
- Future studies could explore the optimal dosing and combination regimens of sonrotoclax with chemotherapy, as well as its potential use in combination with other targeted therapies or immunotherapies for AML
- The study's findings may also have implications for the development of novel agents and treatment strategies for AML, and may lead to increased research into the role of BCL-2 inhibition in AML therapy