Armin Ghobadi

In ZUMA-7 (NCT03391466), axicabtagene ciloleucel (axi-cel) significantly improved outcomes versus second-line (2L) standard of care (SOC) for adults with relapsed/refractory large B-cell lymphoma (LBCL). The optimal management of patients after disease progression or lack of response to 2L therapy remains unclear. Here, we report outcomes among patients who received subsequent anti-lymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7. Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation by randomized 2L arm. In the SOC arm, 127/179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n=68) versus those who did not (n=59) was 6.3 versus 1.9 months, respectively; median OS was 16.3 versus 9.5 months, respectively. In the axi-cel arm, 84/180 randomized patients (47%) received 3L therapy. Median PFS among those who received 3L chemotherapy (n=60) versus cellular immunotherapy (n=8) was 1.7 versus 3.5 months, respectively; median OS was 8.1 months versus not reached, respectively. Of the 60 patients who received 3L chemotherapy, 10 underwent stem cell transplantation (SCT; 9 autologous; 1 allogeneic) after salvage chemotherapy. Median PFS was 11.5 versus 1.6 months, and median OS was 17.5 versus 7.2 months for those who did versus those who did not reach SCT, respectively. Eight patients received 3L cellular immunotherapy after 2L axi-cel. Of these, 6 patients received subsequent SCT in any line, and all 6 were alive at data cutoff. These findings help inform subsequent treatment choices after failure of 2L therapy for relapsed/refractory LBCL.

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting the use of axi-cel in patients with LBCL, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients with R/R LBCL who received axi-cel between 2017-2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 clinical trials, respectively. Adjusted odds ratio (OR) and hazard ratio (HR) for race and ethnicity groups are reported. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37, [95% CI, 0.22-0.63]) and lower complete response rate (OR, 0.57, [95% CI, 0.33-0.97]) than NH-white patients. NH-Black patients also had a shorter progression-free survival versus NH-white (HR, 1.41, [95% CI, 1.04-1.90]) and NH-Asian patients (HR, 1.67, [95% CI, 1.08-2.59]). NH-Asian patients had a longer duration of response compared with NH-white (HR, 0.56, [95% CI, 0.33-0.94]) and Hispanic patients (HR, 0.54, [95% CI, 0.30-0.97]). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade ICANS were observed in NH-white patients compared with other patients. These results provide important context when treating patients with R/R LBCL with axi-cel across different racial and ethnic groups. ZUMA-1 (NCT02348216) and ZUMA-7 (NCT03391466), both registered on ClinicalTrials.gov