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

Autor: Alarcon Tomas A; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Ph.D. Program in Signals Integration and Modulation in Biomedicine, Cell Therapy, and Translational Medicine, University of Murcia, Murcia, Spain.; Department of Hematology, Hospital Universitario Gregorio Marañón, Madrid, Spain., Fein JA; University of Connecticut Medical Center, Farmington, CT, USA., Fried S; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Flynn JR; Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Devlin SM; Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fingrut WB; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Anagnostou T; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, and 2. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Alperovich A; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; BMT and Cellular Therapy Department, Monter Cancer Center, Northshore University Hospital, Lake Success, NY, USA., Shah N; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fraint E; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Division of Pediatric Hematology, Oncology, and Cellular Therapy, The Children's Hospital at Montefiore, Bronx, NY, USA., Lin RJ; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Scordo M; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Batlevi CL; Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Besser MJ; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel.; Ella Lemelbaum Institute for Immuno Oncology, Sheba Medical Center, Tel Hashomer, Israel.; Davidoff Center, Rabin Medical Center, Petach Tikva, Israel., Dahi PB; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Danylesko I; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Giralt S; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Imber BS; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jacoby E; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Kedmi M; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Nagler A; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Palomba ML; Weill Cornell Medical College, New York, NY, USA.; Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Roshal M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Salles GA; Weill Cornell Medical College, New York, NY, USA.; Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sauter C; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Shem-Tov N; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Shimoni A; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Yahalom J; Weill Cornell Medical College, New York, NY, USA.; Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Yerushalmi R; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Shah GL; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Avigdor A; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.; Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel., Perales MA; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. peralesm@mskcc.org.; Weill Cornell Medical College, New York, NY, USA. peralesm@mskcc.org., Shouval R; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. shouvalr@mskcc.org.; Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel. shouvalr@mskcc.org.; Weill Cornell Medical College, New York, NY, USA. shouvalr@mskcc.org.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2023 Jan; Vol. 37 (1), pp. 154-163. Date of Electronic Publication: 2022 Nov 05.
DOI: 10.1038/s41375-022-01739-2
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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