Outcomes of Subsequent Therapies Following Axi-cel for Second-Line Treatment of Relapsed or Refractory LBCL in the ZUMA-7 Study

In the phase 3 ZUMA-7 study (NCT03391466), axicabtagene ciloleucel (axi-cel) significantly improved event-free survival versus second-line (2L) standard of care (SOC) for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL); thus, chimeric antigen receptor T-cell (CAR-T) therapy has been proposed as the new SOC for 2L treatment for eligible patients. However, patients may require additional therapy, and optimal management following 2L therapy remains undefined. Outcomes for patients in ZUMA-7 receiving subsequent treatment were presented at the 64th American Society of Hematology Annual Meeting and Exposition.

Eligible patients were randomized 1:1 to axi-cel or SOC (2-3 cycles of chemotherapy [CT] followed by high-dose chemoimmunotherapy [CIT] with autologous stem-cell transplant [ASCT] for those with partial response [PR] or complete response [CR]). Subsequent therapies and disease assessments were up to investigator discretion. Treatment with third-line (3L) therapy was classified as CT and CIT; for the axi-cel arm, re-treatment with axi-cel was allowed for patients who initially responded. Kaplan-Meier estimates for progression-free survival (PFS) and overall survival (OS) were calculated from 3L treatment initiation. Patients who did not meet the criteria for a PFS event were censored at fourth-line treatment initiation or last known alive date. Patients who received subsequent stem-cell transplant (SCT) while in a response from 3L axi-cel re-treatment were censored at the time of SCT. Best response to subsequent therapy was evaluated.

In the axi-cel arm, 84 of 180 (47%) patients received subsequent therapy; 60 and 8 patients received 3L CT and 3L CIT, respectively. For patients who received 3L CT, overall median (m)PFS was 1.7 months (mo; 95% confidence interval [CI], 1.4-2.0) and mOS was 8.1 mo (95% CI, 5.8-11.5) since 3L treatment initiation, with an objective response rate (ORR) of 25%; CR rate was 13%. For 34 patients who received 3L CT after initial response to 2L axi-cel, overall mPFS was 1.7 mo (95% CI, 1.4-2.4) and mOS was 8.1 mo (95% CI, 6.8-11.9), with an ORR of 32%; CR rate was 18%. Of 60 patients who received 3L CT, 10 patients received subsequent SCT (9 ASCT, 1 allogeneic SCT). For those who received SCT versus those who did not, mPFS was 11.5 mo (95% CI, 2.4-not evaluable [NE]) versus 1.6 mo (95% CI, 1.2-1.8), and mOS was 17.5 mo (95% CI, 2.4-NE) versus 7.2 mo (95% CI, 4.8-9.1).

Of 8 patients in the axi-cel arm who received 3L CIT, 6 received subsequent SCT (1 ASCT, 5 allogeneic SCT) in any line, 3 of which (allogeneic SCT) immediately followed 3L axi-cel. Of 6 patients who received SCT, 5 remained in CR; 1 patient had a PR after axi-cel re-treatment and proceeded to allogeneic SCT with best response of CR but relapsed 7.3 mo afterward. All 6 patients who received SCT were alive at the data cutoff date (median follow-up from 3L treatment initiation, 24.4 mo).

In the SOC arm, 127 of 179 (71%) patients required 3L therapy; of these, 68 received CIT. For patients receiving 3L CIT, mPFS was 6.3 mo (95% CI, 3.4-16.3) and mOS was 16.3 mo (95% CI, 8.7-NE), compared with mPFS and mOS of 1.9 mo (95% CI, 1.1-2.7) and 9.5 mo (95% CI, 6.6-15.4), respectively, for those who did not receive CIT. Of 68 patients who received 3L CIT and were evaluated for response, ORR was 57%; CR rate was 34%.

Subsequent axi-cel re-treatment in ZUMA-7 was found to be feasible, and outcomes for these patients with LBCL appeared improved. While definitive conclusions cannot be made due to the small sample size, re-treatment with CAR-T therapy after initial responses may be a viable option in this setting.


Ghobadi A, Munoz J, Westin J, et al. Outcomes of subsequent anti-lymphoma therapies in patients with large B-cell lymphoma treated with axicabtagene ciloleucel or standard of care in the second-line ZUMA-7 study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Oral presentation 659.

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