Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Authors: Lee Dasom (Caroline) , Kambhampati Swetha , Bobillo Maria Silvina Odstrcil , Adedokun Babatunde , Shadman Mazyar , Olson Amanda L. , Herrera Alex F. , Lee Catherine J. , Jacobson Caron A. , Bye Matthew , Hamadani Mehdi , Kim Soyoung , Dahiya Saurabh , Hu Zhen-Huan , Speth Kelly , To Christina , Mirjah Debbie L. , Best Timothy , Locke Frederick L. , Ahmed Nausheen , Tees Michael T. , Pasquini Marcelo C. , Ahmed Sairah 
Published: December 2024

Introduction
In the Phase 3 ZUMA-7 study (NCT03391466), axi-cel, an autologous anti-CD19 CAR T-cell therapy, showed superior event-free survival (EFS; Locke FL, et al. NEJM 2022), response rate, and overall survival (OS) vs standard of care (Westin JR, et al. NEJM 2023) in transplant-intended R/R LBCL. Axi-cel is approved in many countries for R/R LBCL within 12 mo after first-line therapy. A Phase 2 trial (ALYCANTE; NCT04531046) additionally demonstrated high response and durable remissions in transplant-ineligible pts (Houot R, et al. Nat Med 2023). In the real world, pts receiving second-line (2L) axi-cel may have a broader range of pt and/or disease characteristics that would have precluded eligibility in these trials. This study evaluated early real-world effectiveness and safety outcomes of US pts who received axi-cel as a 2L treatment of R/R LBCL.
Methods
Adult pts with R/R LBCL who received commercial axi-cel in 2L between Apr 2022-July 2023 in the US and enrolled in the CIBMTR® data registry were included. Descriptive statistics summarized baseline pt characteristics and post-infusion outcomes in the overall population, by ZUMA-7 eligibility (adapted to data available in CIBMTR), and in pts with PMBCL. When sufficient data were available, 12-mo data were reported; otherwise, 6-mo data were reported.
Results
Across 89 centers, 446 pts received axi-cel (DLBCL, 78%; PMBCL, 3%; high grade B-cell lymphoma, 18%; follicular lymphoma grade IIIB, 1%). Median age at infusion was 63.9 y (range, 19.5-86.0; 47% ≥65 y); 64% of pts were male; 97% had ECOG 0 or 1; 72% were non-Hispanic White, 12% were Hispanic, 6% were non-Hispanic Asian, and 5% were non-Hispanic Black. Most had ≥1 clinically significant comorbidity (71%; Sorror ML, et al. Blood 2005). Prior to infusion, 48% had elevated lactate dehydrogenase and 25% had complete response (CR) as best response to last line of therapy prior to leukapheresis. Median vein-to-vein time was 29 days (IQR, 27-35). Most received bridging therapy (66%; systemic, 53%; radiation, 16%). Lymphodepleting chemotherapy regimens were mostly cyclophosphamide plus fludarabine (75%) or bendamustine (22%). Half (52%) would have been ineligible for ZUMA-7, mainly due to organ impairment (34%) and prior malignancy (16%).
Among all pts, at a median follow-up of 12.0 mo, objective response rate (ORR) was 79% (95% CI, 75-82), with a CR rate of 64% (95% CI, 60-69). The 12-mo rate (95% CI) of duration of response (DOR) was 66% (59-71), progression-free survival (PFS) was 53% (48-58), EFS was 53% (48-58), and OS was 71% (66-76). Any-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 87% (Grade [Gr] ≥3, 5%) and 50% (Gr ≥3, 22%), respectively. To treat pts with any CRS and/or ICANS (n=398, 89%), tocilizumab, corticosteroids, and anakinra were given to 80%, 65%, and 18%, respectively. Median duration of CRS and ICANS was 5 days (IQR, 4-7) and 6 days (IQR, 3-10), respectively. Prolonged cytopenias (by Day 30; n=440) were reported in 16% of pts (neutropenia, 7%; thrombocytopenia, 11%); infections were reported in 44%. Cumulative incidence of non-relapse mortality at 6 mo was 4%.
When assessed by ZUMA-7 eligibility, ORRs (95% CI) in ineligible pts (n=219; excluding pts with PMBCL) and eligible or unknown pts (n=214) were 79% (72-84) and 79% (73-85), respectively, with CR rates of 63% (56-69) and 65% (58-72). The 12-mo rates (95% CI) of DOR in ZUMA-7 ineligible and eligible or unknown pts were 60% (50-68) and 69% (60-77), PFS was 48% (40-55) and 58% (51-65), EFS was 48% (40-55) and 58% (50-64), and OS was 62% (53-69) and 80% (73-85), respectively. Incidence of any-grade CRS was 88% in ZUMA-7 ineligible pts and 87% in ZUMA-7 eligible or unknown pts.
Among 13 pts with PMBCL, ORR was 69% (95% CI, 39-91); all with CR. The 6-mo rates (95% CI) of DOR, PFS, EFS, and OS were 100%, 68% (36-87), 68% (36-87), and 100%, respectively. Incidence of any-grade CRS and ICANS was 85% (Gr ≥3, 0%) and 54% (Gr ≥3, 9%), respectively. Prolonged cytopenias were reported in 8% of pts. Incidence of infections was 38%.
Conclusions
This is the largest real-world analysis of pts with R/R LBCL who received 2L commercial axi-cel. Despite a broader pt population beyond the ZUMA-7 and ALYCANTE trials, outcomes at median follow-up of 12 mo were consistent with those observed in ZUMA-7.
DCL, SK, and MSOB contributed equally.