CAR T cells for the long run in aggressive B-cell lymphoma.

Abstract

Since first being reported in 2010, 1 Kochenderfer JN Wilson WH Janik JE et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010; 116: 4099-4102 Crossref PubMed Scopus (912) Google Scholar CD19-directed chimeric antigen receptor (CAR) T cells have led a revolution in the treatment of B-cell non-Hodgkin lymphomas. The US Food and Drug Administration have approved three CAR T-cell products for the treatment of relapsed or refractory aggressive B-cell lymphomas: tisagenlecleucel, axicabtagene ciloleucel, and lisocabtagene maraleucel. All three showed high rates of complete responses in patients with refractory disease in pivotal trials (37 [40%] of 93, 2 Schuster SJ Bishop MR Tam CS et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019; 380: 45-56 Crossref PubMed Scopus (1179) Google Scholar 59 [58%] of 101, 3 Locke FL Ghobadi A Jacobson CA et al. Long-term safety and efficacy of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019; 20: 31-42 Summary Full Text Full Text PDF PubMed Scopus (693) Google Scholar and 136 [53%] of 256, 4 Abramson JS Palomba ML Gordon LI et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396: 839-852 Summary Full Text Full Text PDF PubMed Scopus (271) Google Scholar respectively), taking into account different patient selection and trial designs in each study. In parallel, real-world data have emerged for these products, showing similar overall responses of 61·8% (95% CI 53·6–69·6) for tisagenlecleucel and 70% (61–78) for axicabtagene ciloleucel, and complete responses in 60 (39%) of 152 patients for tisagenlecleucel and 61 (50%) of 122 patients for axicabtagene ciloleucel. 5 Pasquini MC Hu ZH Curran K et al. Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Adv. 2020; 4: 5414-5424 Crossref PubMed Scopus (71) Google Scholar , 6 Jacobson CA Hunter BD Redd R et al. Axicabtagene ciloleucel in the non-trial setting: outcomes and correlates of response, resistance, and toxicity. J Clin Oncol. 2020; 38: 3095-3106 Crossref PubMed Scopus (72) Google Scholar Real-world studies have supported the efficacy and safety of CD19-directed CAR T-cell therapies, including in many patients who would not have been eligible for the pivotal clinical trials. Among patients treated with axicabtagene ciloleucel in the ZUMA-1 study 7 Jacobson C Locke FL Ghobadi A et al. Long-term survival and gradual recovery of B cells in patients with refractory large B cell lymphoma treated with axicabtagene ciloleucel (axi-cel). Blood. 2020; 136: 40-42 Google Scholar with at least 4 years of follow-up (median follow-up 51·1 months), the median overall survival was 25·8 months, and the 4-year estimated overall survival was 44%. The reported duration of follow-up in the JULIET study was relatively short until now. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 studyTisagenlecleucel shows durable activity and manageable safety profiles in adult patients with relapsed or refractory aggressive B-cell lymphomas. For patients with large B-cell lymphomas that are refractory to chemoimmunotherapy or relapsing after second-line therapies, tisagenlecleucel compares favourably with respect to risk–benefit relative to conventional therapeutic approaches (eg, salvage chemotherapy). Full-Text PDF