Acute and delayed cytopenias following CAR T-cell therapy: an investigation of risk factors and mechanisms

Abstract

Prolonged myelosuppression after chimeric antigen receptor (CAR) T-cell therapy is common and poorly understood. A retrospective analysis of 43 patients was conducted to investigate factors contributing to CAR T-cell-related cytopenias. Thirty-five patients were evaluable for analysis of delayed cytopenias occurring after initial hematologic recovery. Time to hematologic recovery (TTHR) was defined as number of days after CAR T-cell infusion for recovery to hemoglobin ≥8.0 g/dL, platelets ≥50.0 k/µL, and neutrophil count ≥1.0 k/µL without transfusions or growth factors for 7 days. Baseline percent bone marrow (BM) malignancy involvement correlated with TTHR (p = .0047). Patients with grades 3–4 cytokine-release syndrome (CRS) had longer TTHR than those with grades 0–2 CRS (p = .0479). Patients who developed prolonged or delayed cytopenias after anti-BCMA CAR T cells had a higher percentage of BM aspirate CAR⁺ cells at 2 months (n = 10; p = .0159).

Keywords:

• Chimeric antigen receptor
• CAR T-cell
• hematologic malignancies
• cytopenia
• bone marrow suppression

Acknowledgments

The authors thank all investigators, research nurses, patient care coordinators, and NIH Clinical Center personnel who assisted in the care of the patients participating in the included clinical trials or otherwise assisted in clinical trial execution. The authors especially thank the patients who participated in these clinical trials and their families.

Author contribution

JNB and JNK performed the data analysis and wrote and edited the manuscript. NL and DN performed laboratory analysis of patient samples and edited and approved the manuscript. AD-F performed hematopathologic analysis of bone marrow specimens, provided images for figures, and edited and approved the manuscript. CMY performed flow cytometry analysis, provided images for figures, and edited and approved the manuscript.

Disclosure statement

JNB: Kyverna Therapeutics, Inc.: scientific advisory committee (unpaid position); NL: Kite, a Gilead Company: Patent and royalties; JNK: Kite, a Gilead company: research funding and royalties on patents. Bristol Myers Squibb: research funding. Kyverna Therapeutics, Inc.: royalties on patents. No other authors have conflicts of interest.

Additional information

Funding

The research reported here was supported by the Intramural Research Program of the NIH and the National Cancer Institute Center for Cancer Research.