Approach to Patients with Acute Myeloid Leukemia in First Relapse: A Practical Guide for Canadian Hematologists

Abstract

Acute myeloid leukemia (AML) is an aggressive and heterogeneous type of blood cancer associated with significant morbidity and mortality. Despite major improvements in the treatment of AML over the last decade, many patients unfortunately present with relapsed or refractory (R/R) disease after first-line standard treatment. With traditional high-intensity induction chemotherapy (IC) for AML, such as the 7+3 regimen, complete remission (CR) rates are about 75–80%, and in those who achieve remission, the relapse rate is approximately 40–50%. With less intensive regimens, such as azacitidine plus venetoclax (Aza-Ven), composite CR rates are about 65–70%, and in those who respond, about half will relapse within 2 years.3 Relapses mainly result from the survival of leukemia stem cells (LSCs), which may acquire additional mutations under the selective pressure of therapy and expand to drive disease recurrence.4 The majority of patients with R/R AML present with adverse-risk genetic features, which are associated with a lower median overall survival (OS) of less than 6 months. With second-line therapy for R/R AML, the overall response rates (ORRs) ranged between 20%–45%,5 underscoring the unmet need regarding the best therapeutic approach for these patients. This review aims to help the reader quickly identify the most common current standard salvage chemotherapy regimens and targeted agents used in the first relapse setting of AML and discuss the ongoing challenges in treating this patient population.