Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma

Ana Alarcon Tomas, Joshua A. Fein, Shalev Fried, Jessica R. Flynn, Sean M. Devlin, Warren B. Fingrut, Theodora Anagnostou, Anna Alperovich, Nishi Shah, Ellen Fraint, Richard J. Lin, Michael Scordo, Connie Lee Batlevi, Michal J. Besser, Parastoo B. Dahi, Ivetta Danylesko, Sergio Giralt, Brandon S. Imber, Elad Jacoby, Meirav KedmiArnon Nagler, M. Lia Palomba, Mikhail Roshal, Gilles A. Salles, Craig Sauter, Noga Shem-Tov, Avichai Shimoni, Joachim Yahalom, Ronit Yerushalmi, Gunjan L. Shah, Abraham Avigdor, Miguel Angel Perales, Roni Shouval

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - 2022
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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