Managing Post-Immunotherapy Relapse in B-ALL: Antigen Escape and Lineage Switch
This clinical review outlines a systematic approach to diagnosing and treating relapse after CD19-directed immunotherapy in B-cell ALL, covering CD19-positive relapse, CD19-negative antigen escape, and lineage switch to AML. The authors highlight the essential roles of next-generation sequencing and multiparameter flow cytometry in monitoring myeloid marker emergence and detecting antigen loss. Treatment options discussed include CAR-T reinfusions, humanised CAR constructs, and alternative antigen-targeted therapies such as inotuzumab.
The original study
How I treat postimmunotherapy relapsed B-ALL.
- Authors
- Lamble AJ, Kovach AE, Shah NN
- Journal
- Blood
- Type
- Journal Article, Case Reports, Review, Research Support, N.I.H., Intramural
- PMID
- 39046821
Original abstract
Despite significant advancements in single-antigen targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL), nonresponse and relapse persist as major challenges. Antigen escape after blinatumomab or CD19-directed chimeric antigen receptor (CAR) T cells (CD19-CAR), as CD19-negative B-ALL or lineage switch (LS) to acute myeloid leukemia, present diagnostic and treatment complexities. Given the poor outcomes for patients experiencing a postinfusion relapse, particularly those with loss of the target antigen, a strategic approach to diagnosis and treatment is imperative. In this discussion, we outline a systematic approach to managing postimmunotherapy events, categorized by CD19-positive relapse, CD19-negative relapse, and LS. We explore treatment modalities including CD19-CAR reinfusions, humanized CAR constructs, combinatorial strategies, and alternative antigen-targeted therapies, such as blinatumomab and inotuzumab. Challenges in diagnosis, particularly with antigen-escape, are addressed, highlighting the role of next-generation sequencing and multiparameter flow cytometry for myeloid marker monitoring.