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Published on: February 17, 2022
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Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells
Adam J Lamble1, Regina M Myers2, Agne Taraseviciute3
1Division of Hematology/Oncology, University of Washington, Seattle Children's Hospital, Seattle, WA.
Blood Advances
|April 28, 2022
Summary
Relapse after CAR T-cell therapy for B-ALL is common. Preinfusion factors predict relapse type: CD19pos, CD19neg, or lineage switch, guiding future interventions.
Area of Science:
- Oncology
- Immunotherapy
- Hematology
Background:
- Relapse after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) is a significant clinical challenge.
- Understanding relapse patterns, including CD19-positive, CD19-negative, and lineage switch, is crucial for improving patient outcomes.
Purpose of the Study:
- To identify and validate preinfusion risk factors associated with specific relapse phenotypes after CAR T-cell therapy in pediatric and young adult patients with r/r B-ALL.
- To inform the development of targeted interventions to mitigate relapse risk.
Main Methods:
- A multicenter, retrospective review of 420 patients with r/r B-ALL treated with a murine-based CD19-CAR construct.
- Analysis of preinfusion clinical and molecular characteristics to identify risk factors for CD19pos, CD19neg, and lineage switch relapse.
Main Results:
- Of 420 patients, 166 (39.5%) relapsed: 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) lineage switch (LS).
- Greater prior complete remissions predicted CD19pos relapse.
- High disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct predicted CD19neg relapse.
- KMT2A rearrangement was the sole predictor for LS relapse.
Conclusions:
- Preinfusion risk factors can predict specific relapse patterns following CAR T-cell therapy in r/r B-ALL.
- Lineage switch relapse is associated with dismal survival, highlighting the need for novel therapeutic strategies.
- Further investigation into relapse prevention strategies, including consolidative hematopoietic stem cell transplantation, is critical.
