A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed/refractory follicular lymphoma

Abstract

Background: In the ZUMA-5 trial (Clinical trials identification: NCT03105336 ), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data. Research design and methods: The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3 rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response rate was compared using a weighted logistic regression. Time-to-event outcomes were evaluated using a Cox regression. Results: For SCHOLAR-5, the sum of weights for the 143 patients was 85 after SMR weighting, versus 86 patients in ZUMA-5. The median follow-up was 29.4 months and 25.4 months for ZUMA-5 and SCHOLAR-5, respectively. The hazard ratios for overall survival and progression-free survival were 0.52 (95% confidence interval (CI): 0.28–0.95) and 0.28 (95% CI: 0.17–0.45), favoring axi-cel. Conclusion: This updated analysis, using a longer minimum follow-up than a previously published analysis, shows that the improved efficacy of axi-cel, relative to available therapies, in r/r FL is durable.

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

“… 15 However, corroborating these findings, the retrospective analysis comparing findings in ZUMA-5 with other standard treatment results for FL (SCHOLAR-5) after 2 years of follow-up demonstrated significant benefit in PFS with axi-cel compared with the standardized mortality-weighted control cohort (39.6 vs 12.7 months; hazard ratio, 0.28). 16 Median OS was not yet reached in patients with FL in this study, even though most patients received ≥3 prior lines of therapy (exclusive of single-agent anti-CD20 antibody), an indicator of poor prognosis in the modern era. 3 Additionally, more than half of the patients had POD24, and the PFS for these patients at high risk appeared largely similar to those without POD24.…”

“… 13 Of note, median PFS for patients with bendamustine exposure >6 months of leukapheresis compared favorably with historical outcomes. 16 Taken together, these results suggest that bendamustine-based therapies may be carefully considered in patients who are likely to need CAR T-cell therapy in the near future, especially those at high risk. 21 , 22 Further assessments on larger patient cohorts are needed to determine whether and to what extent the inferior outcomes in this subset of patients are due to the unfavorable disease biology vs prior treatment with bendamustine and to identify an optimal washout period.…”

Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

“…Grade ≥ 3 cytokine release syndrome (CRS) occurred in 6% of the patients, and grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 15% [ 28 , 29 ]. A propensity score matching comparison between patients with R/R FL treated in the ZUMA-5 setting and patients treated with SOC therapies strongly favored axi-cel both in terms of PFS (HR 0.28, 95% CI: 0.17–0.45) and OS (HR 0.52, 95% CI: 0.28–0.95) [ 30 ].…”

Burden of Illness in Follicular Lymphoma with Multiple Lines of Treatment, Italian RWE Analysis

“…Patients who experience relapsed or refractory disease need to proceed beyond more lines of therapy [9,10]. The management of these patients has evolved over time thanks to the introduction of new classes of agents, such as phosphoinositide 3-kinase inhibitors (idelalisib) [11], epigenetic therapies [12], immunomodulators (lenalidomide) [13,14], and chimeric antigen receptor T cells [15].…”