Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia

• Authors: Muna Qayed, Emory University; Marie Bleakley, Fred Hutchinson Cancer Research Center; Nirali N Shah, National Cancer Institute, NIH, Bethesda
• Journal Title: CURRENT OPINION IN HEMATOLOGY
• Volume: Volume 28, Number 6
• Publisher: LIPPINCOTT WILLIAMS & WILKINS | 2021-11-01, Pages 373-379
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/MOH.0000000000000685
• Subjects: Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; chimeric antigen receptor T-cell; hematopoietic stem cell transplantation; leukemia; MINIMAL RESIDUAL DISEASE; HIGH-RISK; FREE SURVIVAL; YOUNG-ADULTS; B-ALL; CHILDREN; CD19; BLINATUMOMAB; CHEMOTHERAPY; ADOLESCENTS

Abstract

Purpose of reviewTo discuss the curative potential for chimeric antigen receptor T-cell (CAR-T) therapy, with or without consolidative hematopoietic stem cell transplantation (HCT) in the treatment of children and young adults with B lineage acute lymphoblastic leukemia (B-ALL).Recent findingsCAR-T targeting CD19 can induce durable remissions and prolong life in patients with relapsed/refractory B-ALL. Whether HCT is needed to consolidate remission and cure relapse/refractory B-ALL following a CD19 CAR-T induced remission remains controversial. Preliminary evidence suggests that consolidative HCT following CAR-T in HCT-naïve children improves leukemia-free survival. However, avoiding HCT-related late effects is a desirable goal, so identification of patients at high risk of relapse is needed to appropriately direct those patients to HCT when necessary, while avoiding HCT in others. High disease burden prior to CAR-T infusion, loss of B-cell aplasia and detection of measurable residual disease by flow cytometry or next-generation sequencing following CAR-T therapy associate with a higher relapse risk and may identify patients requiring consolidative HCT for relapse prevention.SummaryThere is a pressing need to determine when CD19 CAR-T alone is likely to be curative and when a consolidative HCT will be required. We discuss the current state of knowledge and future directions.