OUTCOME OF LARGE B‐CELL LYMPHOMA PATIENTS FAILING CD19 TARGETED CAR‐T THERAPY

Background: Despite high initial response rates, most patients with relapsed/refractory (r/r) large B-cell lymphoma receiving CD19 targeted CAR-T therapy will progress or relapse. There are limited data available on post-CAR-T management and outcomes. We provide detailed outcome analyses from a prospective national cohort of lymphoma patients progressing after licenced CD19 CAR-T. Methods: We analysed consecutive patients with r/r large B-cell lymphoma who received axicabtagene ciloleucel or tisagenlecleucel between Feb 2019 - Dec 2020 across 10 UK centres and were primary refractory or relapsed after infusion. Results: Of 294 patients infused with CAR-T, 153 (52%) progressed. 143 (93%) of progressions occurred within 6 months (m) of infusion, 79 (52%) after an initial response (30 CR, 49 PR). The median time to progression was 2.4 m (IQR: 0.99 – 13.3), 3.2 m (IQR: 2.9 – 5.1) after initial CR vs. 3.0 m (IQR: 2.4 – 3.1) after PR. 82/153 (54%) patients received further treatment: 10 radiotherapy (RT) alone, 31 R-bendamustine/polatuzumab vedotin (RBP), 13 R-lenalidomide, 13 standard chemotherapies, 6 checkpoint inhibition (CPI), 3 CD20xCD3 bispecific antibodies, 2 BTKi, 4 other treatments. 10 patients underwent allogeneic transplant. Patients undergoing treatment for post-CAR-T relapse were younger (med. age 56y vs. 60y; p = 0.03), had better ECOG performance status pre-infusion (0/1: 96% vs. 76%; p = 0.005), and more likely to have had transient responses to CAR-T (61% vs. 41%; p = 0.007) compared to patients not considered for further treatment. With a median follow-up of 9.6 m, median OS post CAR-T progression was 3.7 m (95% CI: 3 – 6), with 1.4 m (95% CI: 1 – 2) for patients not receiving further treatment, and 7.8 m (95% CI: 6 – 10) for treated patients [11.0 m for patients responding vs. 4.5 m for non-responders]. The overall response rate to post-CAR-T treatment was 39% (28/72) and within groups of 10+ patients as follows: 15/31 (48%) for RBP, 2/13 (15%) for standard chemotherapy, and 2/11 (18%) for R-lenalidomide, with a median OS post progression of 10 m (95% CI: 8 – 12), 5.2 m (2 – NR) and 7.3 m (3 – NR), respectively. 18 (22%) patients achieved CR following post-CAR-T therapy (3 after RT, 10 RBP, 2 CPI, 1 bispecific antibodies, 2 chemotherapy), 9 of which underwent allogeneic transplant. Median OS after achieving CR was 12.3 m (5 – NR). Updated response- and survival data will be provided at the meeting. Discussion: This large national real-world cohort demonstrates the poor outcome of lymphoma patients failing CD19 CAR-T, with almost half of patients not given further treatment. Response to post-CAR-T therapies is limited indicating an area of unmet need in those fit for further treatment and highlighting the importance of appropriate patient counselling. Access to effective novel agents may increase the numbers who can be bridged to allogeneic transplant and potentially improve long-term outcomes. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract A. Kuhnl Consultant or advisory role: Kite, Novartis, Celgene Honoraria: Kite, Novartis Educational grants: Kite A. A. Kirkwood Consultant or advisory role: Kite M. O'Reilly Honoraria: Kite, Novartis Educational grants: Kite, Novartis R. Sanderson Honoraria: Kite, Novartis E. Tholouli Consultant or advisory role: Kite, Novartis Honoraria: Kite, Novartis A. Patel Honoraria: Kite, Novartis C. Besley Honoraria: Kite, Novartis S. Iyengar Consultant or advisory role: Kite, Takeda, Beigene Honoraria: Kite, Takeda Educational grants: Abbvie A.-L. Latif Honoraria: Kite, Jazz, Daiichi Sankyo, Novartis, Amgen, AbbVie, Astellas W. Osborne Honoraria: Roche, Takeda, Pfizer, Servier, Kite Gilead, MSD, Novartis, Beigene, Astra Zeneca, Syneos, Autolus G. Collins Consultant or advisory role: Kite Honoraria: Kite, Novartis A. McMillan Consultant or advisory role: Roche Honoraria: Roche Educational grants: Roche S. Chaganti Honoraria: Kite, Novartis T. Menne Honoraria: Kite, Amgen, Novartis, Pfizer, Celgene, Daiichi Sankyo, Atara, Takeda, Janssen, Roche, Servier Research funding: Janssen, Astra Zeneca, Novartis 16-ICML SPECIAL LECTURE: LYMPHOMA TREATMENT IN DEVELOPING COUNTRIES