Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease.

Autor: Jen WY; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kadia TM; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., DiNardo CD; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Issa GC; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Short NJ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Yilmaz M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Borthakur G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Ravandi F; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Daver NG; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Jul; Vol. 205 (1), pp. 30-47. Date of Electronic Publication: 2024 May 09.
DOI: 10.1111/bjh.19519
Abstrakt: The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1 mut and KMT2A-rearranged AML. With so many new drugs approved, the number of potential combinatorial approaches to leverage the maximal benefit of these agents has increased dramatically, while at the same time introducing clinical challenges, such as key preclinical and clinical data supporting the development of combinatorial therapy, how to optimally combine or sequence these novel agents, how to optimise dose and duration to maintain safety while enhancing efficacy, the optimal duration of therapy and the role of measurable residual disease in decision-making in both intensive and low-intensity therapy settings. In this review, we will outline the evidence leading to the approval of key agents in AML, their on-label current approvals and how they may be optimally combined in a safe and deliverable fashion to further improve outcomes in AML.
(© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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