Outcomes of subsequent therapies after 2L axi-cel or SOC in R/R LBCL: ZUMA-7 study

In the phase III ZUMA-7 (NCT03391466) study, axicabtagene ciloleucel (axi-cel) demonstrated a higher event-free survival and overall response rate (ORR), as well as a significantly improved overall survival (OS) vs standard-of-care (SOC) as second-line (2L) therapy in adult patients with relapsed/refractory large B-cell lymphoma (LBCL); however, the optimal management after 2L therapy in patients who do not yield a response or disease progression is unclear.

Here, we summarize an article published by Ghobadi et al.¹ in Blood Advances on the outcomes of subsequent anti-lymphoma therapies after 2L axi-cel or SOC in the ZUMA-7 study.

Study methods¹

• The full study design of ZUMA-7 is detailed here
• In the SOC arm, third-line (3L) therapy included cellular immunotherapy or other treatments (non-cellular immunotherapy).
• In the axi-cel arm, 3L therapy included chemotherapy, cellular immunotherapy, or other treatments.
• Study endpoints included investigator-assessed progression-free survival (PFS), OS, and best response to subsequent therapy.

Key findings¹

• A total of 359 patients were randomized to axi-cel (n = 180) and SOC (n = 179) arms in ZUMA-7.
• In total, 127 out of 179 patients in the SOC arm received subsequent 3L therapies.
• In total, 84 out of 180 patients in the axi-cel arm received subsequent 3L therapies.
• Among patients in the SOC arm who received 3L cellular immunotherapy (n = 68) vs those who did not (n = 59):

• • The median PFS was 6.3 months vs 1.9 months, respectively
  • The median OS was 16.3 months vs 9.5 months, respectively
  • The 12-month PFS was 41% vs 20%, respectively
  • The 12-month OS was 56% and 41%, respectively
  • In the SOC arm, the ORR was 57% (complete response [CR] rate, 34%)
• Among patients in the axi-cel arm who received third-line cellular chemotherapy (n = 60) vs chemoimmunotherapy (n = 8) vs other therapies (n = 16):
  • The median PFS was 1.7 months vs 3.5 months vs 3.5 months, respectively
  • The median OS was 8.1 months vs not reached vs 8.6 months, respectively
  • In the axi-cel arm who received 3L cellular chemotherapy, the ORR was 25% (CR rate, 13%)
• Of the patients receiving 3L chemotherapy, ten underwent stem cell transplantation:
  • The median PFS for those who underwent stem cell transplantation vs those who did not was 11.5 months vs 1.6 months, respectively
  • The median OS was 17.5 months vs 7.2 months, respectively
  • ORR was 80% (CR rate, 60%) vs 14% (CR rate, 4%), respectively

Key learnings
Despite the limited sample size, these results suggest that better outcomes are achieved when cellular therapies are given as 2L vs 3L therapies in patients with relapsed/refractory LBCL. 3L cellular therapy could be a feasible option in patients with LBCL progression after 2L axi-cel in those with an initial response; however, further studies are needed.