Characteristics and Outcomes of Patients Receiving Bridging Therapy While Awaiting Manufacture of Standard of Care Axicabtagene Ciloleucel CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Results from the US Lymphoma CAR-T Consortium

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.245-245
• Main Authors: Jain, Michael D., Jacobs, Miriam T., Nastoupil, Loretta J., Spiegel, Jay Y., Feng, Gao, Lin, Yi, Lunning, Matthew A., Dahiya, Saurabh, Lekakis, Lazaros J, Reagan, Patrick M, Oluwole, Olalekan O., McGuirk, Joseph P., Deol, Abhinav, Goy, Andre, Hill, Brian T., Munoz, Javier, Chavez, Julio, Rapoport, Aaron P., Vose, Julie M, Miklos, David B, Neelapu, Sattva S, Bennani, N. Nora, Andreadis, Charalambos, Sehgal, Alison R., Ghobadi, Armin, Locke, Frederick L.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-129624

MDJ and MTJ contributed equally; FLL and AG contributed equally. Introduction Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are autologous anti-CD19 CAR T-cell therapies approved for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL) who have failed at least two lines of systemic therapy. In the ZUMA-1 trial that led to axi-cel approval, the median time between apheresis and delivery of CAR T cells to the treating facility was 17 days (Neelapu, Locke et al. NEJM 2018). Bridging therapy, defined as lymphoma therapy given between apheresis and the start of lymphodepleting chemotherapy, was not permitted on ZUMA-1. By contrast, the pivotal JULIET trial for tisa-cel (Schuster et al. NEJM 2019) had a median time from enrollment to infusion of 54 days and 92% of patients received bridging therapy. Whether bridging therapy affects lymphoma CAR T outcomes is unknown. Here we evaluate patients receiving bridging therapy for axi-cel in a large multicenter cohort. Methods and Results The US Lymphoma CAR T Consortium includes seventeen US academic centers that contribute data from lymphoma patients treated with standard of care (SOC) CAR T-cell therapy independently of manufacturers. As of 8/31/2018, 300 patients were apheresed with intent to manufacture SOC axi-cel for LBCL. Of the 23 patients that underwent apheresis for axi-cel and did not receive it, 20 had lymphoma progression or death that precluded CAR T infusion, of which 16 received bridging therapy. In this study, we analyze the modified intent-to-treat (mITT) population of 276 patients receiving CAR T infusion with a median follow up of 9 months. In this group, 146 (53%) patients received bridging therapy while 130 (47%) patients received no bridging therapy. Bridging therapy consisted of steroids alone (n = 35, 24%), chemotherapy (n = 73, 50%), radiation (n = 24, 16%), or targeted therapies (n = 14, 10%). At baseline, a higher proportion of patients in the bridging therapy group had an ECOG score of 2 - 4 vs. 0 - 1 (bridging 24.8%, no bridging 6.1%, p