Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Authors to whom correspondence should be addressed.
Cancers 2025, 17(5), 779; https://doi.org/10.3390/cancers17050779
Submission received: 28 December 2024
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Revised: 21 February 2025
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Accepted: 22 February 2025
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Published: 25 February 2025
(This article belongs to the Special Issue Drug Development for Acute Lymphoblastic Leukemia)
Simple Summary
Despite high remission and survival rates in younger adults with B-cell acute lymphoblastic leukemia (B-ALL), managing relapsed disease across all age groups and optimizing treatment for older patients in both frontline and relapsed settings remain significant challenges. This manuscript explores advancements beyond conventional chemotherapy, focusing on antibody-based therapies such as blinatumomab and inotuzumab ozogamicin, CAR T-cell therapy, and emerging strategies targeting apoptosis, epigenetics, and the mTOR pathway to exploit therapeutic vulnerabilities in B-ALL.
Abstract
Despite notable progress in managing B-cell acute lymphoblastic leukemia (B-ALL) over recent decades, particularly in pediatric cohorts where the 5-year overall survival (OS) reaches 90%, outcomes for the 10–15% with relapsed and refractory disease remain unfavorable. This disparity is further accentuated in adults, where individuals over the age of 40 years undergoing aggressive multiagent chemotherapy continue to have lower survival rates. While the adoption of pediatric-inspired treatment protocols has enhanced complete remission (CR) rates among younger adults, 20–30% of these patients experience relapse, resulting in a subsequent 5-year OS rate of 40–50%. For relapsed B-ALL in adults, there is no universally accepted standard salvage therapy, and the median OS is short. The cornerstone of B-ALL treatment continues to be the utilization of combined cytotoxic chemotherapy regimens to maximize early and durable disease control. In this manuscript, we go beyond the multiagent chemotherapy medications developed prior to the 1980s and focus on the incorporation of antibody-based therapy for B-ALL with an eye on existing and upcoming approved indications for blinatumomab, inotuzumab ozogamicin, other monoclonal antibodies, and chimeric antigen receptor (CAR) T cell products in frontline and relapsed/refractory settings. In addition, we discuss emerging investigational therapies that harness the therapeutic vulnerabilities of the disease through targeting apoptosis, modifying epigenetics, and inhibiting the mTOR pathway.
