Outcomes by prior lines of therapy (LoT) in ZUMA-1, the pivotal phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients (Pts) with refractory large B cell lymphoma.

3039 Background: In ZUMA-1 (NCT02348216), axi-cel, an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated significant benefit in patients (pts) with refractory large B cell lymphoma with an objective response rate (ORR) of 82% (complete response [CR] 58%; Neelapu & Locke et al. NEJM. 2017). These results supported the recent approval of axi-cel by the US FDA for the treatment of adult pts with relapsed or refractory large B cell lymphoma after ≥ 2 prior lines of systemic therapy. Here, we assessed outcomes of axi-cel by prior lines of therapy (LoT) in pts from Phases 1 and 2 of ZUMA-1. Methods: Pts with refractory large B cell lymphoma were leukapheresed and received 2 × 106 CAR T cells/kg after low-dose conditioning (Neelapu & Locke et al. NEJM 2017). Pts were evaluated by number of prior LoT: 2 – 3 vs ≥ 4. Autologous stem cell transplant (ASCT) was considered a prior LoT. Results: As of 8/11/17, median follow-up was 15.4 mo for the 108 pts treated with axi-cel. Sixty-two (57%) pts had 2 – 3 prior LoT and 43 (40%) had ≥ 4. Pts with 2 – 3 and ≥ 4 prior LoT had median ages of 60 and 55 y, 65% and 47% of pts had ECOG performance status 1, 18% and 42% had prior ASCT, and 76% and 93% had disease stage III/IV, respectively. ORRs were 94% and 67% for pts with 2 – 3 and ≥ 4 prior LoT, respectively, with CR rates of 65% and 53%; 44% and 42% of pts had ongoing responses as of the data cutoff (Table). Overall survival (OS) at 12 mo was 65% and 51% for pts with 2 – 3 and ≥ 4 prior LoT, respectively. Grade ≥ 3 treatment-emergent adverse events were reported for nearly all (100% and 93%) pts with 2 – 3 and ≥ 4 LoT, with similar rates of Grade ≥ 3 cytokine release syndrome (11% and 12%) and neurologic events (32% and 30%). There were 1 and 3 Grade 5 AEs unrelated to disease progression in the 2 – 3 and ≥ 4 LoT groups, respectively. Conclusions: Axi-cel demonstrated long-term clinical benefit for pts with refractory large B cell lymphoma regardless of the number of prior LoT. Drs Locke and Neelapu contributed equally. Clinical trial information: NCT02348216.Response, % (95% CI) LoT 2 – 3 (n = 62) ≥ 4 (n = 43) ORR 94 (84 – 98) 67 (51 – 81) CR rate 65 (51 – 76) 53 (38 – 69) Ongoing ORR 44 (31 – 57) 42 (27 – 58) 6-mo PFSa 49 (36 – 61) 51 (35 – 65) 12-mo OSa 65 (51 – 75) 51 (35 – 65) aKM estimate