Real‐World Early Outcomes of Axicabtagene Ciloleucel for Relapsed or Refractory (R/R) Follicular Lymphoma (FL)

Abstract

Background: Axicabtagene ciloleucel (axi-cel) is an autologous CAR T-cell therapy approved for adult patients (pts) with R/R FL after ≥2 lines of systemic therapy. In the primary analysis of the pivotal ZUMA-5 trial, 94% of pts who received axi-cel to treat R/R FL achieved an objective response, with a 79% CR rate (Jacobson et al. Lancet Oncol. 2022). Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 6% and 15% of pts, respectively. Here, we present real-world outcomes of pts receiving axi-cel for R/R FL, including those who would have been ineligible for ZUMA-5. Methods: A total of 230 pts from 72 US centers receiving first axi-cel for R/R FL in the real-world setting between March 2021 and October 2022 were identified from the CIBMTR registry. The following pts were excluded: no consent, prior non-transplant cellular therapy, and FL grade 3b or 3a/3b unspecified. Of the 230 pts, 151 had post-infusion assessments and were included in the analysis of outcomes. Effectiveness outcomes were ORR, CR, DOR, PFS and OS. Adverse events included CRS, immune effector cell–associated neurotoxicity syndrome (ICANS) and prolonged cytopenia. Results: Of the 230 pts, median age was 62 years and 60% were male. Prior to infusion, 98% had an ECOG performance score of 0–1, 33% had elevated LDH, and 66% were chemo-resistant. Clinically significant comorbidities were present in 74% of the pts. Ninety-two (40%) pts would have been ineligible for ZUMA-5, mainly due to comorbidities. Pts had a median of 4 (range 1–13) lines of prior therapy including 14% who also underwent prior ASCT. Median time from leukapheresis to infusion was 28 days (IQR 26–34). 9% of pts received bridging therapy. Outcomes were analyzed among the 151 pts with follow-up (median 6.2 mo). ORR and CR rates were 93% (95% CI: 88%–97%) and 84% (95% CI: 77%–89%), respectively. Estimated PFS and OS at 6 mo were 88% (95% CI: 81%–92%) and 96% (95% CI: 91%–98%), respectively. Grade ≥3 CRS (ASTCT consensus) and ICANS (ASTCT consensus) occurred in 2% (95% CI: 0%–6%) and 13% (95% CI: 8%–19%) of pts, respectively. Median cumulative incidence estimate for CRS resolution was 5 days; for ICANS resolution was 4 days. Among pts alive at Day 30 (n = 150), 11% experienced prolonged cytopenia (4% neutropenia, 9% thrombocytopenia). PFS and OS at 6 mo were comparable regardless of ZUMA-5 eligibility, while pts eligible for ZUMA-5 had fewer Grade ≥3 ICANS (10% vs. 16%) and more rapid ICANS resolution (92% vs. 71% resolved ≤2 weeks). Pts aged ≥65 versus <65 years had comparable effectiveness and safety profiles. Conclusion: This is the first report on axi-cel to treat R/R FL in real-world settings. Despite a broader pt population, early results demonstrate effectiveness and safety profiles consistent with those observed in the ZUMA-5 trial. The intent is to present findings from an updated dataset with longer follow-up. Overall, these findings support the continued broad use of axi-cel to treat R/R FL. Encore Abstract - previously submitted to ASCO 2023 and EHA 2023 The research was funded by: The research was funded by: Kite, a Gilead Company. Keywords: Cellular therapies, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. C. Jacobson Consultant or advisory role: Kite, a Gilead Company, Novartis, BMS/Celgene, Instil Bio, ImmPACT Bio, Lonza, Ipsen, Epizyme, Bluebird bio, and Daiichi Sankyo Honoraria: Kite, Novartis, BMS/Celgene, Instil Bio, ImmPACT Bio, Lonza, Ipsen, Epizyme, BlueBird Bio, and Daiichi Sankyo Research funding: Kite and Pfizer M. T. Hemmer Employment or leadership position: Kite, a Gilead Company Consultant or advisory role: Pfizer Honoraria: Pfizer Z. Hu Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Science M. Frank Employment or leadership position: Roche/Genentech Consultant or advisory role: EcoR1, BRVL Stock ownership: Roche/Genentech Research funding: Allogene, Kite, a Gilead Company, and Adaptive Biotechnology L. Popplewell Consultant or advisory role: Seattle Genetics, Novartis Honoraria: Seattle Genetics, Pfizer, Hoffman-Roche Other remuneration: Seattle Genetics, Pfizer, Hoffman-Roche Y. Lin Consultant or advisory role: Kite, a Gilead Company, Gilead, Celgene/BMS, Juno/BMS, BlueBird Bio, Janssen, Legend BioTech, Gamida Cells, Novartis, Iovance, Takeda, Fosun Kite, and Pfizer Research funding: Kite, Gilead, Celgene/BMS, BlueBird Bio, Janssen, Legend Biotech, Merck, Takeda, and Boston Scientific T. Best Employment or leadership position: Kite, a Gilead Company Stock ownership: Bristol Myers Squibb S. Beygi Employment or leadership position: Kite, a Gilead Company Stock ownership: Kite Educational grants: Kite H. Miao Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead C. Fu Employment or leadership position: Kite, a Gilead Company Stock ownership: Kite, Amgen Other remuneration: Cellares F. Sun Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead H. Xu Employment or leadership position: Kite, a Gilead Company M. C. Pasquini Consultant or advisory role: Amgen, Medigene, and Pfize Honoraria: Celgene Research funding: Bristol-Myers Squibb, Kite, a Gilead Company, and Novartis