Massachusetts General Hospital, Boston, MA
Matthew J. Frigault , Theresa Amoloja , Lea Micaletti Burke , Rodica Morariu-Zamfir , Valkal Bhatt , Kristen Bibeau , Xiao Ying Tang , Amy Moskop , Richard T. Maziarz , John F. DiPersio
Background: The engineered T-cell products axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) are FDA approved for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), respectively. This study investigated real-world rates of CRS and ICANS following CAR-T. Methods: This study analyzed CIBMTR data of US SUBJ receiving axi-cel or brexu-cel for any indication from Oct 2020–Dec 2021 with ≥1 follow-up visit. CRS and ICANS were graded per American Society for Transplantation and Cellular Therapy consensus guidelines. Results: 927 SUBJ (median age, 63 y; men, 65%) from 87 centers were analyzed. Most received axi-cel (76%), 83% of whom had DLBCL or transformed follicular lymphoma (tFL); 24% received brexu-cel (MCL). Most SUBJ had Ann Arbor stage III/IV (63%), no active central nervous system disease (84%), and refractory disease at CAR-T infusion (66%). Among all 589 SUBJ with DLBCL/tFL who received axi-cel, 54% achieved complete response, 17% partial response, and 6% stable disease. 89/715 SUBJ with available data received treatment for CRS prevention, mostly tocilizumab alone (80% [71/89]) or in combination (3% [3/89]). Overall, 766 SUBJ (83%) developed CRS (grade ≥3, 64 [8%]; Table). Of the 89 SUBJ who received CRS prevention treatment, 78% developed CRS, with 3% (3/89) having grade ≥3. 77% of SUBJ with CRS received CRS treatment, 97% of whom received tocilizumab (alone or in combination [eg, with corticosteroids]). Most (64%) SUBJ with grade 1 CRS received treatment, 63% of whom received tocilizumab alone. ICANS occurred in 424/876 SUBJ with ICANS data (48%; Table), of whom 205 (48%) had grade ≥3. ICANS treatment was reported and administered to 86% of SUBJ with ICANS, 92% of whom received corticosteroids. Conclusions: CRS and ICANS incidence rates were consistent with previously published literature and highlight potential burdens of CAR-T. In addition, the treatment landscape for CRS is changing; SUBJ with grade 1 CRS often received treatment. These data will inform the design of future studies aimed at preventing and treating CAR-T toxicities.
CRS* | ICANS† | |||||
---|---|---|---|---|---|---|
All SUBJ n=927 | Axi-cel n=707 | Brexu-cel n=220 | All SUBJ n=876 | Axi-cel n=664 | Brexu-cel n=212 | |
Median (range) age, y | 63 (19–89) | 62 (19–88) | 65 (34–89) | 63 (19–89) | 62 (19–88) | 65 (34–89) |
Incidence, % | 83 | 81 | 86 | 48 | 45 | 60 |
Grade 1/≥2 | 44/39 | 45/36 | 39/47 | 14/35 | 13/32 | 17/43 |
Grade 3/4/5 | 4/2/1 | 3/2/1 | 5/3/1 | 15/6/1 | 14/6/<1 | 18/9/2 |
Time to onset, median (range), d | 4 (1–157) | 4 (1–157) | 5 (1–46) | 7 (1–101) | 7 (1–101) | 7 (1–31) |
<72 h onset, % | 32 | 32 | 32 | 7 | 8 | 6 |
Grade ≥2, % | 17 | 16 | 20 | 6 | 6 | 4 |
Duration, median (range), d | 5 (0–175) | 5 (0–40) | 4 (0–175) | 7 (1–98) | 6 (1–67) | 8 (1–98) |
All SUBJ with data available for *CRS or †ICANS.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2022 ASCO Annual Meeting
First Author: Nishant Munugala
2023 ASCO Annual Meeting
First Author: Priyanshu Nain
2023 ASCO Annual Meeting
First Author: Kenneth Barker
2024 ASCO Annual Meeting
First Author: Allison Marie Winter