PMID- 36260735 OWN - NLM STAT- MEDLINE DCOM- 20230103 LR - 20230209 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 7 IP - 1 DP - 2023 Jan 10 TI - Toxicity and efficacy of CAR T-cell therapy in primary and secondary CNS lymphoma: a meta-analysis of 128 patients. PG - 32-39 LID - 10.1182/bloodadvances.2022008525 [doi] AB - Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 chimeric antigen receptor (CAR) T cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We, therefore, performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS] and cytokine release syndrome [CRS]) as well as response rates in these 2 populations. Seventy percent of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the patients with PCNSL, 56% achieved a complete remission (CR) with 37% remaining in remission at 6 months. Similarly, 47% of patients with SCNSL had a CR, with 37% in remission at 6 months. In a large meta-analysis of central nervous system (CNS) lymphomas, toxicity of anti-CD19-CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL. CI - (c) 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - Cook, Michael R AU - Cook MR AUID- ORCID: 0000-0002-6171-9647 AD - Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC. FAU - Dorris, C Scott AU - Dorris CS AUID- ORCID: 0000-0002-4664-6793 AD - Dahlgren Memorial Library, Georgetown University, Washington, DC. FAU - Makambi, Kepher H AU - Makambi KH AD - Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC. FAU - Luo, Yutong AU - Luo Y AD - Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC. FAU - Munshi, Pashna N AU - Munshi PN AD - Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC. FAU - Donato, Michelle AU - Donato M AD - John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ. FAU - Rowley, Scott AU - Rowley S AUID- ORCID: 0000-0002-3299-835X AD - Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC. FAU - Saad, Ayman AU - Saad A AUID- ORCID: 0000-0003-0003-0130 AD - Division of Hematology, The Ohio State University, Columbus, OH. FAU - Goy, Andre AU - Goy A AUID- ORCID: 0000-0001-5125-6522 AD - John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ. FAU - Dunleavy, Kieron AU - Dunleavy K AD - Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC. FAU - Ali, Alaa AU - Ali A AUID- ORCID: 0000-0003-1813-515X AD - Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (Antigens, CD19) RN - 0 (cell-associated neurotoxicity) SB - IM MH - Humans MH - Antigens, CD19 MH - *Central Nervous System Neoplasms/therapy/pathology MH - Cytokine Release Syndrome MH - Immunotherapy, Adoptive/adverse effects MH - *Lymphoma, Large B-Cell, Diffuse/pathology MH - *Lymphoma, Non-Hodgkin MH - *Neoplasms, Second Primary MH - *Neurotoxicity Syndromes PMC - PMC9813524 COIS- Conflict-of-interest disclosure: K.D. served on the advisory board/consulting for AstraZeneca, Beigene, AbbVie, Daiichi Sankyo, ADC Therapeutics, Incyte, Morphosys, Genmab. P.N.M. served on the advisory board for Incyte; consultancy: Incyte; speakers bureau: Incyte, Kite Pharma. A.G. acted in a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Celgene, Hoffmann-La Roche, Janssen, Kite, Morphosys, Allopex, Gilead, Novartis, Vincerx, Resilience, received research funding (institutional) from Acerta, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, Hoffmann-La Roche, Infinity, Janssen, Karyopharm, Kite, Morphosys, Pharmacyclics, Seattle Genetics, Verastem. A.S. served as a consultant (Kite/Gilead, Magenta Therapeutics, Incyte Pharmaceuticals, CareDx) and received royalty fees from In8Bio Inc. A.A. served on the advisory board/consulting for Incyte. The remaining authors declare no competing financial interests. EDAT- 2022/10/20 06:00 MHDA- 2022/12/31 06:00 PMCR- 2022/10/21 CRDT- 2022/10/19 14:22 PHST- 2022/09/15 00:00 [accepted] PHST- 2022/07/08 00:00 [received] PHST- 2022/10/20 06:00 [pubmed] PHST- 2022/12/31 06:00 [medline] PHST- 2022/10/19 14:22 [entrez] PHST- 2022/10/21 00:00 [pmc-release] AID - 486840 [pii] AID - 10.1182/bloodadvances.2022008525 [doi] PST - ppublish SO - Blood Adv. 2023 Jan 10;7(1):32-39. doi: 10.1182/bloodadvances.2022008525.