Beygi, Sara

Background: Axicabtagene ciloleucel (axi-cel), an autologous chimeric antigen receptor (CAR) T-cell therapy, achieved an overall response rate (ORR) of 94% and a complete response (CR) rate of 79% in patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more prior lines of therapy in the ZUMA-5 trial ( Jacobson et al. Lancet Oncol. 2022). Since its FDA approval in March 2021, there has been little evidence on comparative effectiveness (CE) studies of axi-cel vs standard-of-care (SoC), except ones using ZUMA-5 and historical SCHOLAR-5 data (eg, Ghione et al. Blood. 2022). This study was aimed to address this evidence gap in CE of axi-cel vs SoC used to treat r/r FL in real-world settings. Methods: The two data sources in this study were patients who received commercial axi-cel between March 2021 and May 2023 from the CIBMTR and patients who received historical SoC (eg, chemotherapy, anti-CD20 mAb + chemotherapy, immunomodulatory imide drugs) between July 2014 and December 2020 from SCHOLAR-5, which served as an external control of ZUMA-5 trial. The index date was defined as the initiation date of either the infusion for axi-cel patients or the last eligible systemic therapy for SoC patients. Patients were included if they were age ≥ 18, had documented r/r FL with histological grade 1, 2 or 3a, and received at least 2 prior lines of therapy at the index. Patients were excluded if they had transformed diffused large B-cell lymphoma, central nervous system involvement, prior receipt of CAR T or other non-CAR T cellular therapies or allogeneic stem cell transplant, or no post-index information on outcomes. Four effectiveness outcomes were ORR, CR rate, progression-free survival (PFS), and overall survival (OS). Imbalance in observed prognostic risk factors between the two was adjusted via a propensity score analysis using the standard mortality ratio weighting (SMRW). The primary analyses included weighted univariable analysis and multivariable logistic (ORR and CR rate) or Cox (PFS and OS) regressions that were adjusted for the covariates after the SMRW. A sub-analysis of patients age ≥ 65 was conducted using the same methods as the primary analyses. Results: The unweighted study cohort included 376 patients, in which 256 (68%) received axi-cel . Thepatients who received axi-cel were more likely to be younger (median age 61 for axi-cel vs 67 for SoC), have grade 3a FL (37% vs 12%), received 3 or more prior lines of therapy (83% vs 58%), or remained refractory to the last prior therapy (79% vs 73%) vs those who received SoC. The imbalance in the observed prognostic risk factors was mitigated via the SMRW. The weighted univariable analysis, in which the sample size by treatment reflected the SMRW, is shown in Table 1. In patients of all ages, ORR was 92% in axi-cel vs 67% in SoC, and CR rate was 84% vs 37%. Because of varying follow-up lengths by treatment (median 7 months for axi-cel and 37 months for SoC), survival outcomes were reported at month 6, at which time PFS rate was 88% in axi-cel vs 64% in SoC and OS rate was 97% vs 85%. The corresponding proportions for patients age ≥ 65 were similar to those reported for patients of all ages. In the weighted multivariable regressions, axi-cel was associated with statistically significantly better outcomes by all 4 effectiveness measures vs SoC (Table 1). Specifically, in patients of all ages, the odds ratios for axi-cel were 4.93 (95% CI, 2.35−10.34) for ORR and 16.72 (95% CI, 7.03−39.73) for CR rate, and the hazard ratios for axi-cel were 0.41 (95% CI, 0.22−0.77) for PFS and 0.15 (95% CI, 0.06−0.34) for OS. Similar to the patients of all ages in the primary analyses, patients age ≥ 65 in the sub-analysis also demonstrated improved outcomes associated with axi-cel (Figure 1). Conclusions: This study showed that patients with r/r FL after two or more prior lines of therapy treated with axi-cel experienced better outcomes compared with patients treated with SoC, and that older patients also benefited significantly from axi-cel. These findings suggest that axi-cel addresses an important unmet medical need in patients with r/r FL. Future research should include longer follow-up data on outcomes of axi-cel and CE of axi-cel vs other contemporary SoC therapies.

7509 Background: Axicabtagene ciloleucel (axi-cel) is an autologous CAR T 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. 2022). Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events occurred in 6% and 15% of pts, respectively. Here, we present the 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 pts 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 estimates of CRS resolution was 5 days and 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 within 2 weeks). Pts aged ≥ 65 vs < 65 years had comparable effectiveness and safety profiles. Conclusions: 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 at ASCO. Overall, these findings support the continued broad use of axi-cel to treat r/r FL.