Journal Article

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

Torka, Pallawi, Ma, Shuo, Kittai, Adam S., Winter, Jane N., Stephens, Deborah M., Shah, Harsh, Shah, Nirav N., Nastoupil, Loretta, Gordon, Leo I., David, Kevin A., Hashmi, Hamza, Nizamuddin, Imran A., Karmali, Reem, Zurko, Joanna, Shouse, Geoffrey, Epperla, Narendranath, Feng, Lei, Cohen, Jonathon B., Hess, Brian, Fitzgerald, Lindsey, Romancik, Jason T., Patel, Romil, Ollila, Thomas, Lee, Catherine J., Reneau, John, Barta, Stefan K., Annunzio, Kaitlin, Ahmed, Sairah, Danilov, Alexey V.

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antigens, CD19 / Apheresis / B-cell lymphoma / Cancer Research / CAR-T / Cell therapy / Central Nervous System / Central Nervous System Neoplasms - therapy / Chimeric antigen receptors / Clinical trials / Cohort analysis / Correspondence / Cytokine Release Syndrome / Development and progression / Early experience / FDA approval / Hematology / Homeopathy / Humans / Immunotherapy, Adoptive - adverse effects / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, Large B-Cell, Diffuse / Materia medica and therapeutics / Medical prognosis / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Meninges / Neoplasms, Second Primary / Nervous system / Neurotoxicity / Non-Hodgkin's lymphomas / Oncology / Outcomes / Patient outcomes / PFS / Receptors, Chimeric Antigen - therapeutic use / Retrospective Studies / Risk factors / SCNSL / Secondary CNS lymphoma / Statistical significance / T cells / Therapeutics