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Opinion|Videos|February 5, 2025

Emerging Combination Strategies and Preclinical Findings

Author(s)Thomas W. LeBlanc, MD, MA, MHS, FAAHPM, FASCO , James Blachly, MD, Aaron Goldberg, MD, PhD Memorial Sloan Kettering Cancer Center

Panelists discuss the interim phase 1a results from KOMET-007 in newly diagnosed NPM1-mutated or KMT2A-rearranged AML, the potential role of ziftomenib combined with 7 plus 3 chemotherapy in standard induction therapy for high-risk acute monocytic leukemia (AML) patients with these mutations, preclinical findings on the combination of ziftomenib and selinexor in NPM1-mutant AML, and the mechanistic synergy between these therapies, exploring their potential in clinical practice and across other AML subtypes.

Episodes in this series

$EP. 1 Treatment Strategies for Relapsed/Refractory AML Patients$

EP. 1 Treatment Strategies for Relapsed/Refractory AML Patients

EP. 2 Treatment Goals and Unmet Needs in R/R AML

EP. 2 Treatment Goals and Unmet Needs in R/R AML

EP. 3 Navigating Challenges in Second- and Third-Line AML Therapy

EP. 3 Navigating Challenges in Second- and Third-Line AML Therapy

EP. 4 Revumenib’s FDA Approval and Clinical Implications

EP. 4 Revumenib’s FDA Approval and Clinical Implications

EP. 5 Efficacy and Potential of Revumenib in KMT2A-Translocated Leukemia

EP. 5 Efficacy and Potential of Revumenib in KMT2A-Translocated Leukemia

EP. 6 Adverse Event Management and Patient Safety With Revumenib

EP. 6 Adverse Event Management and Patient Safety With Revumenib

EP. 7 MRD Testing and the Role of Revumenib in Treatment Response

EP. 7 MRD Testing and the Role of Revumenib in Treatment Response

EP. 8 Integrating Revumenib Into Current R/R AML Treatment Paradigms

EP. 8 Integrating Revumenib Into Current R/R AML Treatment Paradigms

EP. 9 Genetic Testing and Molecular Profiling in AML

EP. 9 Genetic Testing and Molecular Profiling in AML

EP. 10 Emerging Combination Strategies and Preclinical Findings

EP. 10 Emerging Combination Strategies and Preclinical Findings

EP. 11 Future Perspectives on Menin Inhibitors in Acute Leukemias

EP. 11 Future Perspectives on Menin Inhibitors in Acute Leukemias

EP. 12 Closing Perspectives on R/R AML Treatment Advances

EP. 12 Closing Perspectives on R/R AML Treatment Advances

Video content above is prompted by the following:

Dr. LeBlanc to ask Dr. Thirman: Briefly comment on the presented interim phase 1a results from KOMET-007, in newly diagnosed NPM1-mutated or KMT2A-rearranged AML. (Zeidan, AM, et al. ASH 2024. Oral Abstract 214, Session: 616or pg. 15)

Dr. LeBlanc to ask Dr. Thirman: How does the high efficacy and manageable safety profile of ziftomenib combined with 7 plus +3 chemotherapy impact its potential role in standard induction therapy for newly diagnosed high-risk AML, particularly for patients with NPM1-mutated and KMT2A-rearranged mutations?

Dr. LeBlanc to ask Dr. Mannis: Briefly comment on the preclinical findings presented regarding the combination of ziftomenib and selinexor in NPM1-mutant AML. (Dhiman, S, et al. ASH 2024. Poster Abstract 2768, Session: 604 or pg. 17)

Dr. LeBlanc to ask Dr. Mannis: How does the mechanistic synergy between ziftomenib and selinexor in NPM1-mutant AML inform potential combination strategies in clinical practice, and what are the implications for expanding this approach to other AML subtypes?

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