期刊
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
卷 16, 期 1, 页码 97-111出版社
CURRENT MEDICINE GROUP
DOI: 10.1007/s11899-021-00608-6
关键词
Acute myeloid leukemia; Secondary AML; Hypomethylating agents; Venetoclax; CPX-351; Clinical trials
Secondary acute myeloid leukemia (s-AML) is a distinct subgroup of AML with poor outcomes despite recent advances in treatment. Patients with s-AML who have received prior hypomethylating agent (HMA) therapy have limited treatment options and are underrepresented in clinical trials. Novel therapeutic options for this population are critically needed.
Purpose of Review Secondary AML (s-AML) encompasses a distinct subgroup of AML with either therapy-related AML or AML arising from preexisting myeloid neoplasms. Despite recent advances in the treatment armamentarium of AML, outcomes remain poor in s-AML. The purpose of this review is to highlight distinct characteristics, prognostic factors, and treatment options for patients with s-AML. Further, we focus on a distinctly poor-risk subgroup of s-AML with previous exposure to hypomethylating agents (HMAs) and describe ongoing clinical trials in this patient population. Recent Findings CPX-351 (liposomal daunorubicin and cytarabine) is the first drug approved for s-AML and represents an advancement in the management of fit patients with this subtype of AML. Despite incremental improvement in remission rates and survival, long-term survival remains poor. Patients who have received prior HMAs for antecedent MDS rarely benefit from CPX-351 or other cytotoxic chemotherapy regimens. The approval of venetoclax in combination with azacitidine has led to a paradigm shift in the management of newly diagnosed older unfit AML patients; however, patients with s-AML and prior HMA therapy were excluded from the landmark randomized phase 3 study. Several early phase clinical trials with both low- and high-intensity therapies are ongoing for s-AML patients, though prior HMA exposure limits inclusion in many of these studies that include HMAs. Patients with s-AML previously treated with an HMA have dismal outcomes with standard therapeutic options and are under-represented in clinical trials. Trials investigating novel therapeutic options in this population are critically needed.
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