Contemporary Approach to Acute Myeloid Leukemia Therapy in 2022

Abstract

Recent advances in acute myeloid leukemia biology and drug development have transformed the therapeutic landscape for patients diagnosed with this disease. By harnessing insights from the study of the molecular pathogenesis of the disease, the acute myeloid leukemia treatment armamentarium now extends beyond conventional cytotoxic agents to include targeted therapies, and immunotherapeutics, with multiple novel modalities under investigation. During the past 5 years, recent drug approvals have also focused attention on disease scenarios and patient populations for whom newer therapies might be deployed. In this review, we highlight select acute myeloid leukemia therapies in the frontline setting through the lens of both disease and patient-related factors. Particular emphasis is placed on the assessment of patient fitness, as contemporary acute myeloid leukemia therapy decisions largely hinge on the determination of whether intensive chemotherapy is suitable for a patient. Additionally, we detail scenarios and areas of controversy wherein disease biology may inspire a reframing of traditional intensive treatment philosophies, regardless of patient fitness. Lastly, we provide an overview of emerging agents that are being investigated in the relapsed/refractory setting.

FIGURE 1.. Overview of Recently Approved Agents for Acute Myeloid Leukemia

The schematic shows approval dates and putative mechanism of action of recently approved agents on the AML cell. Agents approved for newly diagnosed or R/R disease are depicted. Venetoclax, glasdegib, and ivosidenib have FDA labels for patients deemed to be ineligible for intensive treatment strategies in the frontline setting. Notably, oral azacitidine is intended for maintenance therapy in patients in complete remission or complete remission with incomplete count recovery following intensive induction chemotherapy and who are not able to complete intensive curative therapy. Abbreviations: AML, acute myeloid leukemia; FDA, U.S. Food and Drug Administration; mIDH1, mutant IDH1; mIDH2, mutant IDH2; R/R, relapsed/refractory; SMO, smoothened.