Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach

Abstract

The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. The notable subsets of AML include acute promyelocytic leukemia (APL), core-binding factor AML (CBF-AML), AML in younger patients fit for intensive chemotherapy, and AML in older/unfit patients (usually at the age cutoff of 60-70 years). We also consider within each subset whether the AML is primary or secondary (therapy-related, evolving from untreated or treated myelodysplastic syndrome or myeloproliferative neoplasm). In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80%. Treatment of CBF-AML with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin (GO) results in estimated 10-year survival rates of ≥75%. In younger/fit patients, the "3+7" regimen (3 days of daunorubicin + 7 days of cytarabine) produces less favorable results (estimated 5-year survival rates of 35%; worse in real-world experience); regimens that incorporate high-dose cytarabine, adenosine nucleoside analogs, and GO are producing better results. Adding venetoclax, FLT3, and IDH inhibitors into these regimens has resulted in encouraging preliminary data. In older/unfit patients, low-intensity therapy with hypomethylating agents (HMAs) and venetoclax is now the new standard of care. Better low-intensity regimens incorporating cladribine, low-dose cytarabine, and other targeted therapies (FLT3 and IDH inhibitors) are emerging. Maintenance therapy now has a definite role in the treatment of AML, and oral HMAs with potential treatment benefits are also available. In conclusion, AML therapy is evolving rapidly and treatment results are improving in all AML subsets as novel agents and strategies are incorporated into traditional AML chemotherapy.

DJ4 Targets the Rho-Associated Protein Kinase Pathway and Attenuates Disease Progression in Preclinical Murine Models of Acute Myeloid Leukemia

“…This can aid in drug development, determining relationships across multiple signaling pathways, and identifying coinciding abnormalities. Mutation-specific targeted therapeutics such as midostaurin, enasidenib, or ivosidenib toward common AML mutations such as FLT3, IDH1, or IDH2 may help improve current therapy for subgroups manifesting these mutations [ 56 , 57 , 58 ]. For many older patients, the recent addition of venetoclax, a BLC2-targeting agent, shows improving outcomes.…”

Platelet Microparticles Decrease Daunorubicin-Induced DNA Damage and Modulate Intrinsic Apoptosis in THP-1 Cells

“…Despite the low mutational burden, there are large variations in transcriptomic and proteomic signatures in AML cells, compared with healthy hematopoietic progenitors, and even between different subclones [ 35 , 36 , 37 ]. Despite increased knowledge in the genomics of AML, treatment strategies have essentially remained unchanged for several decades, with a few exceptions [ 38 ]. Curative treatment, which is restricted to younger patients, consists of intensive chemotherapy with consolidating hematopoietic stem cell treatment for high-risk cases.…”

Targeted Therapies and Druggable Genetic Anomalies in Acute Myeloid Leukemia: From Diagnostic Tools to Therapeutic Interventions

“…Based on this consideration, it could be postulated that identifying “druggable” mutations paves the way for the use of novel targeted therapies [ 12 ]. This Special Issue of Cancers focuses on the novel diagnostic and therapeutic tools for the management of AML with the main aim of improving our knowledge in the field of AML [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

“…More recently, the use of Bcl-2 inhibitors (venetoclax), and IDH inhibitors data have raised hopes for the benefits of targeted therapies in AML. For example, in older/unfit AML patients, hypomethylating agents (HMAs) and venetoclaxare now the new standard of care in this setting [ 12 , 13 , 14 ].…”

“…As far as immunotherapy is concerned, immunotherapy-based protocols have demonstrated modest activity in AML which needs to be confirmed in larger series. In contrast, encouraging results have been observed in acute lymphoblastic leukemia and in non-Hodgkin and Hodgkin lymphoma [ 12 , 13 , 14 ].…”