Toxicities and Response Rates of Secondary CNS Lymphoma After Adoptive Immunotherapy With CD19-Directed Chimeric Antigen Receptor T Cells.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
24 05 2022
24 05 2022
Historique:
received:
10
01
2022
accepted:
11
03
2022
pubmed:
31
3
2022
medline:
26
5
2022
entrez:
30
3
2022
Statut:
ppublish
Résumé
Secondary CNS involvement in systemic B-cell lymphoma (SCNSL) is difficult to treat and displays dismal clinical outcomes. Chimeric antigen receptor (CAR) T cells emerged as a powerful treatment for systemic lymphoma. We aimed to evaluate whether CAR T cells also represent a safe and effective therapy for SCNSL. We retrospectively searched our institutional database for patients with SCNSL treated with CD19-directed CAR T cells. We identified 10 cases, including 7 patients with intraparenchymal lesions and 3 patients with leptomeningeal disease. CNS staging at 1 month after CAR T-cell transfusion showed disease response (stable disease, partial response, and complete response) in 7 patients (70%), including 2 cases of long-lasting complete response (20%). One patient developed pseudoprogression, which resolved under steroids. Response of CNS disease was associated with systemic 1-month response. With a median follow-up of 6 months, median overall and systemic progression-free survival was 7 and 3 months, respectively. Neurotoxic symptoms occurred in 6 patients, with 3 patients developing severe neurotoxicity (American Society for Transplantation and Cellular Therapy grade ≥3). CAR T cells induce considerable antitumor effects in SCNSL, and CNS response reflects systemic response. Neurotoxicity appears similar to previous reports on patients with lymphoma without CNS involvement. CAR T cells may therefore represent an effective and safe therapy for SCNSL.
Sections du résumé
BACKGROUND AND OBJECTIVES
Secondary CNS involvement in systemic B-cell lymphoma (SCNSL) is difficult to treat and displays dismal clinical outcomes. Chimeric antigen receptor (CAR) T cells emerged as a powerful treatment for systemic lymphoma. We aimed to evaluate whether CAR T cells also represent a safe and effective therapy for SCNSL.
METHODS
We retrospectively searched our institutional database for patients with SCNSL treated with CD19-directed CAR T cells.
RESULTS
We identified 10 cases, including 7 patients with intraparenchymal lesions and 3 patients with leptomeningeal disease. CNS staging at 1 month after CAR T-cell transfusion showed disease response (stable disease, partial response, and complete response) in 7 patients (70%), including 2 cases of long-lasting complete response (20%). One patient developed pseudoprogression, which resolved under steroids. Response of CNS disease was associated with systemic 1-month response. With a median follow-up of 6 months, median overall and systemic progression-free survival was 7 and 3 months, respectively. Neurotoxic symptoms occurred in 6 patients, with 3 patients developing severe neurotoxicity (American Society for Transplantation and Cellular Therapy grade ≥3).
DISCUSSION
CAR T cells induce considerable antitumor effects in SCNSL, and CNS response reflects systemic response. Neurotoxicity appears similar to previous reports on patients with lymphoma without CNS involvement. CAR T cells may therefore represent an effective and safe therapy for SCNSL.
Identifiants
pubmed: 35351785
pii: WNL.0000000000200608
doi: 10.1212/WNL.0000000000200608
pmc: PMC9169944
doi:
Substances chimiques
Antigens, CD19
0
Receptors, Antigen, T-Cell
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
884-889Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Cell. 2020 Oct 1;183(1):126-142.e17
pubmed: 32961131
N Engl J Med. 2022 Feb 17;386(7):692-696
pubmed: 34904797
Lancet Haematol. 2021 Feb;8(2):e110-e121
pubmed: 33513372
Cancers (Basel). 2021 May 20;13(10):
pubmed: 34065471
Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24275-24284
pubmed: 31712432
Blood. 2019 May 16;133(20):2212-2221
pubmed: 30808634
Blood. 2019 Sep 12;134(11):860-866
pubmed: 31320380