@article{47633455f42447fb96b39850d6ea75d9,
title = "Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma",
abstract = "Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57–69]). Of 52 post-CAR-T biopsies evaluated by flow cytometry, 49 (94%) expressed CD19. Subsequent anti-cancer treatment was administered in 135/182 (74%) patients with CAR-T treatment failure. Median OS from the first post-CAR-T treatment was 8 months (95%CI 5.6–11.0). Polatuzumab-, standard chemotherapy-, and lenalidomide-based treatments were the most common approaches after CAR-T. No complete responses (CRs) were observed with conventional chemotherapy, while CR rates exceeding 30% were seen following polatuzumab- or lenalidomide-based therapies. Factors associated with poor OS among patients treated post-CAR-T were pre-CAR-T bulky disease (HR 2.27 [1.10–4.72]), lack of response to CAR-T (2.33 [1.02–5.29]), age >65 years (HR 2.65 [1.49–4.73]) and elevated LDH at post-CAR-T treatment (HR 2.95 [1.61–5.38]). The presence of ≥2 of these factors was associated with inferior OS compared to ≤1 (56% vs. 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise.",
author = "{Alarcon Tomas}, Ana and Fein, {Joshua A.} and Shalev Fried and Flynn, {Jessica R.} and Devlin, {Sean M.} and Fingrut, {Warren B.} and Theodora Anagnostou and Anna Alperovich and Nishi Shah and Ellen Fraint and Lin, {Richard J.} and Michael Scordo and Batlevi, {Connie Lee} and Besser, {Michal J.} and Dahi, {Parastoo B.} and Ivetta Danylesko and Sergio Giralt and Imber, {Brandon S.} and Elad Jacoby and Meirav Kedmi and Arnon Nagler and Palomba, {M. Lia} and Mikhail Roshal and Salles, {Gilles A.} and Craig Sauter and Noga Shem-Tov and Avichai Shimoni and Joachim Yahalom and Ronit Yerushalmi and Shah, {Gunjan L.} and Abraham Avigdor and Perales, {Miguel Angel} and Roni Shouval",
note = "Funding Information: This research was supported in part by the Memorial Sloan Kettering Cancer Center Core grant (P30 CA008748) from the National Institutes of Health/National Cancer Institute. RS was supported by the American Society of Transplantation and Cellular Therapy New Investigator Award, the American Society of Hematology Fellow Scholar Award, a grant from the Long Island Sound Chapter, Swim Across America, the Robert Hirschhorn Award, and the Memorial Sloan Kettering Steven Greenberg Lymphoma Research Award. AAT was supported by a grant from the Alfonso Mart{\'i}n Escudero. JAF was supported by an HONORS Award from the American Society of Hematology. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
doi = "10.1038/s41375-022-01739-2",
language = "English (US)",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
}
