The cure of leukemia through the optimist's prism

Abstract

Progress is occurring at a dizzying rate across all leukemias. Since the authors' review of the topic in Cancer in 2018, numerous discoveries have been made that have improved the therapy and outcomes of several leukemia subsets. Hairy cell leukemia is potentially curable with a single course of cladribine followed by rituximab (10‐year survival, ≥90%). Acute promyelocytic leukemia is curable at a rate of 80% to 90% with a nonchemotherapy regimen of all‐trans retinoic acid and arsenic trioxide. The cure rate for core‐binding factor acute myeloid leukemia (AML) is ≥75% with fludarabine, high‐dose cytarabine, and gemtuzumab ozogamicin. Survival for patients with chronic myeloid leukemia is close to that for an age‐matched normal population with BCR‐ABL1 tyrosine kinase inhibitors (TKIs). Chronic lymphocytic leukemia, a previously incurable disease, may now be potentially curable with a finite duration of therapy with Bruton tyrosine kinase inhibitors and venetoclax. The estimated 5‐year survival rate for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) exceeds 70% with intensive chemotherapy and ponatinib, a third‐generation BCR‐ABL1 TKI, and more recent nonchemotherapy regimens using dasatinib or ponatinib with blinatumomab are producing outstanding results. Survival in both younger and older patients with ALL has improved with the addition of antibodies targeting CD20, CD19 (blinatumomab), and CD22 (inotuzumab) to chemotherapy. Several recent drug discoveries (venetoclax, FLT3 and IDH inhibitors, and oral hypomethylating agents) are also improving outcomes for younger and older patients with AML and for those with higher risk myelodysplastic syndrome.

Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

“…The result showed that there was no significant difference in overall survival between the RCN1 high expression group and the RCN1 low expression group. We speculate that this may be related to the fact that the RCN1 high expression group is mainly associated with M3 types and FLT3 mutations, with M3 and FLT3 mutations having a good overall treatment outcome [71,72], leading to an improved survival rate in the high RCN1 group. Despite the relative success of treatment for M3 and FLT3 mutations, relapse remains a major obstacle [73,74].…”

Therapeutic Advances in Immunotherapies for Hematological Malignancies

“…Blinatumomab was approved by the FDA for MRD-positive acute lymphoblastic leukemia (ALL) after chemotherapy. Furthermore, chemotherapy-free regimens combining blinatumomab and tyrosine kinase inhibitors are becoming a frontline option for Philadelphia chromosome–positive ALL [ 61 ]. On the other hand, the combination of inotuzumab ozogamicin (InO), an ADC that covalently conjugates calicheamicin to a humanized anti-CD22 antibody, and salvage chemotherapy (mini-hyper-fractionated cyclophosphamide, vincristine, and dexamethasone [mini-hyper-CVD]) with or without blinatumomab was superior to InO or the chemotherapy alone in relapsed or refractory ALL [ 62 ].…”

Pharmaceutical/Clinical Strategies in the Treatment of Acute Promyelocytic Leukemia: All-Trans Retinoic Acid Encapsulation by Spray-Drying Technology as an Innovative Approach–Comprehensive Overview

“…APL was reported as a rapidly fatal disease until the late 1980s [ 7 ]. Currently, it is considered the most curable subtype of AML with survival rates of 80% to 90%, with the combination of the all-trans-RA and arsenic trioxide (non-chemotherapy regimen) [ 8 , 9 ]. Eventually, the combination of these compounds and chemotherapy was also considered in the treatment of APL [ 7 , 9 , 10 , 11 ].…”