Cytotoxic therapy in acute myeloid leukemia: not quite dead yet

Abstract

Given the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients. Indeed, the future likely lies in combinations of therapies that act with a spectrum of mechanisms. Using a case-based format, this review will outline current treatment expectations for patients according to karyotypic risk and familiarize readers with the basis for common induction choices. Relapsed/refractory disease may be especially amenable to interventions with novel agents or clinical trials; however, there are still some patients who most benefit from intensive chemotherapy. This review will outline risk systems that help the practitioner identify those with the best chances for response and survival. Finally, clinical tools, including geriatric assessments and comorbidity calculators, may help clinicians recognize patients for whom disease risk and comorbidity tip the balance against classical chemotherapy, a frequent challenge for those who treat this devastating disease.

Low-intensity regimens versus standard-intensity induction strategies in acute myeloid leukemia

“…ICT continues to play an important role in the treatment of elderly patients with AML and represents an effective option for the growing number of allogeneic SCT candidates. 70 The recent development of novel and effective combination regimens based on HMAs or LDAC in combination with venetoclax challenges the current intensive versus nonintensive dilemma and raises the possibility of replacing ICT as standard care in the near future. 71 It also opens new avenues for further therapeutic improvements based on the addition of targeted drugs such as FLT3 or IDH1 and IDH2 inhibitors, which are just a few notable examples among many other novel compounds.…”

Emerging agents and regimens for treatment of relapsed and refractory acute myeloid leukemia

“…Since the early 1970s, intensive cytotoxic treatment has been the standard of care for AML. Despite some limitations, it is still the best choice for achieving remission, prolonging life, and bridging to allo-HSCT for the ultimate cure [132]. Early chemotherapy drugs were mostly antimetabolites designed to select and damage rapidly dividing leukemia cells rather than the relatively stationary normal cells [133].…”

EVI-1-Mediated Up-Regulation of lncRNA TUG1 Interacts with miR-186-5p to Promote Proliferation and Drug Resistance in Pediatric Acute Myeloid Leukemia

“…Despite considerable improvements in AML remedy including targeted drugs, the overall prognosis for AML is still hard to be estimated, and the ve-year survival rate is only 20-40% [3]. During the recent decades, traditional cytotoxic chemotherapy remains one of the major therapies for AML [4]. Currently, adriamycin (ADR) was a widely used clinical chemotherapeutic agent for AML [5].…”