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Multicenter Study
. 2023 Nov 9;16(1):111.
doi: 10.1186/s13045-023-01508-3.

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

Narendranath Epperla  1 , Lei Feng  2 , Nirav N Shah  3 , Lindsey Fitzgerald  4 , Harsh Shah  4 , Deborah M Stephens  4 , Catherine J Lee  4   5 , Thomas Ollila  6 , Geoffrey Shouse  7 , Alexey V Danilov  7 , Kevin A David  8   9 , Pallawi Torka  9   10 , Hamza Hashmi  11 , Brian Hess  11 , Stefan K Barta  12 , Jason T Romancik  13 , Jonathon B Cohen  13 , Kaitlin Annunzio  14 , Adam S Kittai  14 , John Reneau  14 , Joanna Zurko  3 , Imran A Nizamuddin  15 , Jane N Winter  15 , Leo I Gordon  15 , Shuo Ma  15 , Romil Patel  2 , Loretta Nastoupil  2 , Sairah Ahmed #  16 , Reem Karmali #  15
Affiliations
Multicenter Study

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

Narendranath Epperla et al. J Hematol Oncol. .

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.

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Conflict of interest statement

NE: Research funding: Beigene; Speakers Bureau for Beigene, Incyte, and Novartis; Honoraria/consulting/ad boards for Merck, ADC Therapeutics, Ipsen, Lilly, and Novartis N.N.S reports consultancy or advisory committee participation with Miltenyi Biotec, Lilly Oncology, BMS/Juno, Galapagos, Gilead/Kite, Abbvie, Incyte, Seattle Genetics. He has research funding from both Miltenyi Biotec and Lilly Oncology and is on the scientific advisory board for Tundra Therapeutics. HS: Advisory Boards: ADC Therapeutics, Seagen, AbbVie DMS: has received consulting fees from Abbvie, AstraZeneca, Beigene, BMS, Celgene, Eli Lilly, Genentech, Janssen. DMS has received institutional research funding from AstraZeneca, Novartis. CJL: Research Funding from Incyte Corp; Consulting fees from Incyte Corp, Sanofi, Fresenius Kabi; Advisory Boards for Kite Pharma, BMS, Incyte Corp, Kadmon, Sanofi; Speaker Panel: Kite Pharma; Clinical Trial Steering Committee from Incyte Corp. TAO: Research funding from Loxo Oncology. Consulting fees and research funding from ONO Pharmaceuticals. Consulting fees from ADC therapeutics. GS: Advisory boards: Kite, Beigene, Astra Zeneca; Speakers Bureau: Kite, Beigene AVD has received consulting fees from Abbvie, AstraZeneca, BeiGene, Bristol Meyers Squibb, Genentech, GenMab, Incyte, Janssen, Lilly Oncology, MEI Pharma, Merck, Nurix and Prelude and has ongoing research funding from Abbvie, AstraZeneca, Bayer Oncology, Beigene, Bristol Meyers Squibb, Cyclacel, GenMab, Lilly Oncology, MEI Pharma, Morphosys and Nurix. PT: Consultancy: TG Therapeutics, ADC Therapeutics, Genentech, GenMab, Seagen and Lilly Oncology HH: Consultancy/ ad boards: Janssen, BMS, GSK; Speakers Bureau: Karyopharm, GSK, Janssen, Amgen SKB: Honoraria: Acrotech, Affimed, Daiichi Sankyo, Kyowa Kirin, Janssen, Seagen JBC: Consultant/Advisor: Astra Zeneca, Abbvie, BeiGene, Janssen, Loxo/Lilly, Kite/Gilead, ADCT; Research Funding: LLS, Genentech, AstraZeneca, Novartis, Loxo/Lilly, BMS/Celgene ASK: Research funding from AstraZeneca and BeiGene. Advisory boards for AstraZeneca, Abbvie, BeiGene, Bristol-Myers Squibb, Janssen, Kite a Gilead Company, Lox@Lilly. Speakers bureau for BeiGene. JR: Research funding: Merck, Corvus Pharmaceuticals, Kymera Therapeutics; Consulting: Acrotech biopharma, Kyowa Kirin. JNW: Research funding and honoraria from Merck; Research funding to spouse from Cellectis, Daiichi Sankyo, Rafael, Forty Seven/Gilead, Astellas; Research funding and consultancy fees to spouse from Novartis; Consultancy fees to spouse from Astellas, Ariad/Takeda, CVS/Caremark, Curis, Jazz Pharmaceuticals, King Biotherapeutics, and Rigel Pharmaceuticals. SM: Research funding: Abbvie, AstraZeneca, BeiGene, Janssen, Juno, Loxo, TG Therapeutics. Speakers Bureau: AstraZeneca, BeiGene, Lilly. Advisory boards: Abbvie, AstraZeneca, BMS, Genentech, Janssen SA: Research support to institution for clinical trials from Nektar, Merck, Xencor, Chimagen and Genmab, has membership on Chimagen scientific advisory committee, she serves on Data Safety Monitoring Board for Myeloid Therapeutics; she is a consultant for ADC therapeutics, KITE/Gilead RK: Advisory Board: BMS, Gilead Sciences./Kite Pharma, Janssen, Karyopharm, Pharmacyclics, Morphosys, Epizyme, Genentech/Roche, EUSA, Calithera; Grants/Research Support: BMS, Takeda, BeiGene, Gilead Sciences/Kite, Calithera. Speakers Bureau: AstraZeneca, BeiGene, Morphosys

Figures

Fig. 1
Fig. 1
Survival analysis of patients undergoing CAR-T for SCNSL, A PFS B OS
See this image and copyright information in PMC

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