Real-world data indicates that bridging therapy administered prior to axicabtagene ciloleucel (axi-cel) does not significantly improve efficacy or safety outcomes in patients with relapsed/refractory large B-cell lymphoma (LBCL). The findings, derived from a Center for International Blood and Marrow Transplant Research (CIBMTR) observational database analysis, were presented at the 2023 American Society of Hematology Annual Meeting. While initial assessments suggested potential differences, these were negated after adjusting for patient and disease imbalances.
Impact of Bridging Therapy on Response Rates
The real-world study revealed that patients who received bridging therapy had an overall response rate (ORR) of 70% with axi-cel, including a complete response (CR) rate of 51%. In contrast, patients who did not undergo bridging therapy experienced an ORR of 79%, with a CR rate of 64%. The 3-year duration of response (DOR) rates in the bridging therapy and non–bridging therapy arms were 40% and 49%, respectively. The rates of relapse or progressive disease (PD) at 3 years were 62% and 49% in patients who received and did not receive bridging therapy, respectively.
Median progression-free survival (PFS) was 3.6 months (95% CI, 3.2-4.8) in patients who received bridging therapy, compared to 14.7 months (95% CI, 10.3-19.1) in those who did not. Median overall survival (OS) was 13.4 months (95% CI, 10.7-18.6) and 32.7 months (95% CI, 27.4-41.1), respectively. However, after inverse probability of treatment weighting (IPTW) and multivariable adjustment, no significant difference in axi-cel effectiveness outcomes was found between the two groups. The adjusted ORs/HRs for ORR, PFS, and OS were 0.81, 1.13 (95% CI, 0.94-1.36), and 1.11 (95% CI, 0.92-1.34), respectively.
Investigator Insights
According to Dr. Michael R. Cook, lead study author and assistant professor at the Perelman School of Medicine at the University of Pennsylvania, high disease burden was associated with more bridging therapy use, potentially contributing to worse outcomes in the initial assessment. However, adjusted survival curves showed no statistical difference in PFS and OS between the IPTW bridging therapy and non–bridging therapy groups.
Study Design and Patient Characteristics
The study prospectively collected data from adult LBCL patients treated with axi-cel in the third-line or later settings in the United States between 2017 and 2020 through the CIBMTR registry. The analysis included 1307 patients, with 430 having received bridging therapy and 877 not. Primary efficacy outcomes included ORR, CR, DOR, PFS, relapse/progression, and OS. Key safety outcomes were cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), prolonged thrombocytopenia and neutropenia, non-relapse mortality (NRM), and clinically significant infections.
Safety Outcomes and Bridging Therapy Types
Safety analysis after IPTW showed similar rates of CRS (12% with bridging therapy; 10% without), ICANS (30%; 24%), and infections at 100 days (34%; 29%). However, bridging therapy was associated with a higher incidence of prolonged neutropenia (12% vs 5%; adjusted OR, 2.23) and thrombocytopenia (36% vs 16%; adjusted OR, 2.33). The most common bridging therapies were chemotherapy plus an anti-CD20 monoclonal antibody (58%), non-chemotherapy bridging therapy (23%), and chemotherapy without an anti-CD20 monoclonal antibody (13%).
Impact of Bridging Therapy Response
Patients who responded to bridging therapy experienced increased CRs (HR, 2.00), median PFS (HR, 0.69), and median OS (HR, 0.59) following axi-cel administration. The frequency of any-grade ICANS events also decreased in this population (HR, 0.51).
