Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development
by
,
Michele Stanchina
1,†
,
Deborah Soong
1,2,†,
Binbin Zheng-Lin
3,
Justin M. Watts
4 and
Justin Taylor
4,* 1
Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
2
Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
3
Department of Medicine, Icahn School of Medicine Mount Sinai West-Morningside, New York, NY 10025, USA
4
Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Cancers 2020, 12(11), 3225; https://doi.org/10.3390/cancers12113225
Submission received: 6 October 2020
/
Revised: 26 October 2020
/
Accepted: 28 October 2020
/
Published: 1 November 2020
Simple Summary
Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults, with an average first diagnosis at age 68, and has historically carried poor prognosis due to various genetic alterations and abnormalities that complicate approaches to treatment. Recently, numerous advancements have been made within the realm of AML therapy, including genetically targeted therapies against FLT3, IDH1/2 and tumor protein p53 (TP53), antibody-drug conjugates, and immunotherapies. Alongside these developments in targeted therapies, we have acquired a better understanding of mechanisms of resistance against conventional therapies that have been in use for decades. The goal of our review is to serve as a guide in the latest targeted and immunotherapeutic drugs available, as well as those currently in the pipeline. We review their specific mechanisms, their characteristic properties, indications for use, outcomes in efficacy in clinical trials prior to approval by the FDA, and their usage in combination with other available therapies.
Abstract
Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy comprised of various cytogenetic and molecular abnormalities that has notoriously been difficult to treat with an overall poor prognosis. For decades, treatment options were limited to either intensive chemotherapy with anthracycline and cytarabine-based regimens (7 + 3) or lower intensity regimens including hypomethylating agents or low dose cytarabine, followed by either allogeneic stem cell transplant or consolidation chemotherapy. Fortunately, with the influx of rapidly evolving molecular technologies and new genetic understanding, the treatment landscape for AML has dramatically changed. Advances in the formulation and delivery of 7 + 3 with liposomal cytarabine and daunorubicin (Vyxeos) have improved overall survival in secondary AML. Increased understanding of the genetic underpinnings of AML has led to targeting actionable mutations such as FLT3, IDH1/2 and TP53, and BCL2 or hedgehog pathways in more frail populations. Antibody drug conjugates have resurfaced in the AML landscape and there have been numerous advances utilizing immunotherapies including immune checkpoint inhibitors, antibody-drug conjugates, bispecific T cell engager antibodies, chimeric antigen receptor (CAR)-T therapy and the development of AML vaccines. While there are dozens of ongoing studies and new drugs in the pipeline, this paper serves as a review of the advances achieved in the treatment of AML in the last several years and the most promising future avenues of advancement
Keywords:
novel therapeutics AML; FLT3; IDH1/2; CD33; BCL2; CD47; CD123; hedgehog; anti-body drug conjugate; immunotherapy
