An update of current treatments for adult acute myeloid leukemia

Abstract

Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents.

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

“…Allogeneic hematopoietic stem cell transplantation can be curative for certain patients with AML; however, very few patients are candidates for this procedure (7,8). Patients over 60 years of age have a worse prognosis due to both chemoresistance and intolerance to intensive chemotherapy, with a median survival of 5-10 months (3,5,9,10). Hence, there is an urgent need for the development of safer and more effective therapeutics for AML.…”

Antibody darts on target for acute myelogenous leukemia

“…AML has always been a daunting disease to treat. Apart from the identification of a small percentage of individuals with good risk features who respond to specific therapeutic approaches and specific treatment strategies, no substantial improvements in therapy have been achieved for decades for the majority of individuals developing AML (5,6). While chemotherapy can achieve durable remissions in younger patients with favorable risk leukemia characteristics, individuals over 60 years, who represent the majority of patients with AML and the closely associated disease myelodysplastic syndrome (MDS), have poorer outcomes with leukemia-free survivals measured more frequently in months not years.…”

IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML

“…4 Despite many clinical trials have been conducted over the last two decades, the standard current treatment in AML remains unchanged, and relies on intensive induction chemotherapy based on nucleoside analogs such as Ara-C or fludarabine and anthracyclines such as idarubicin and daunorubicin followed by high doses Ara-C consolidation. 41 Although complete remission rates (CRR) of ~80% are commonly achieved with conventional chemotherapy, 4,42 the median survival time is short and the outcome of relapsed patients is dismal. 43-45 Novel agents or better treatment combinations/schedules with higher efficacy and less toxicity are therefore in high demand for de novo and relapsed AML.…”