Outcomes of patients with secondary central nervous system lymphoma following CAR T-cell therapy: a multicenter cohort study

J Hematol Oncol. 2023 Nov 9;16(1):111. doi: 10.1186/s13045-023-01508-3.

Abstract

Chimeric antigen receptor T-cell therapy (CAR-T) has been successful in treating relapsed/refractory B-cell lymphomas. However, its role in the treatment of diseases involving the central nervous system (CNS) is not well studied. We performed a multicenter retrospective cohort study to evaluate the outcomes of patients with secondary CNS lymphoma (SCNSL) who received CAR-T. Eligibility required active CNSL at the time of apheresis. The objectives included evaluation of overall survival (OS), progression-free survival (PFS), identification of predictors of complete response (CR) post-CAR-T, and assessment of risk factors for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Sixty-one patients were included in the analysis. The overall response rate was 68% with a CR rate of 57%. In the multivariable analysis, patients who experienced any grade CRS had higher odds of achieving CR (OR = 3.9, 95% CI = 1.01-15.39, p = 0.047). The median PFS was 3.3 months (95% CI = 2.6-6.0 months) with 6- and 12-month PFS rates of 35% and 16%, respectively. The median OS was 7.6 months (95% CI = 5.0-13.5 months) with 6- and 12-month OS rates of 59% and 41%, respectively. Any grade CRS and ICANS were 70% (n = 43) and 57% (n = 34), respectively with grade ≥ 3 CRS and ICANS rates of 16% and 44%. Factors associated with increased risk of CRS and ICANS included receiving axi-cel or having leptomeningeal ± parenchymal + CNS involvement, respectively. Despite achieving high response rates, most patients experience early relapse or death following CAR-T in SCNSL. The current study provides a benchmark for future trials exploring novel therapeutic options in SCNSL.

Keywords: CAR-T; OS; Outcomes; PFS; SCNSL; Secondary CNS lymphoma.

Publication types

  • Multicenter Study
  • Letter

MeSH terms

  • Antigens, CD19
  • Central Nervous System
  • Central Nervous System Neoplasms* / therapy
  • Cytokine Release Syndrome
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma*
  • Lymphoma, Large B-Cell, Diffuse*
  • Neoplasms, Second Primary*
  • Receptors, Chimeric Antigen* / therapeutic use
  • Retrospective Studies

Substances

  • cell-associated neurotoxicity
  • Receptors, Chimeric Antigen
  • Antigens, CD19