The largest study yet comparing chimeric antigen receptor (CAR) T-cell therapy with the previous standard of care (SOC) in patients with refractory large B-cell lymphoma (LBCL) found significant benefit to CAR T-cell therapy in patients with refractory diffuse LBCL.
Within the CAR-T cohort, the study also compared axicabtagene ciloleucel and tisagenlecleucel, the two CAR T-cell products targeting CD19 that have been approved in Europe for refractory diffuse LBCL (in the US, a third product, lisocabtagene maraleucel, is also approved). The comparison showed that axicabtagene ciloleucel offered better efficacy but with increased toxicity, compared with tisagenlecleucel.
The results were published in Frontiers in Immunology in a paper by Mariana Bastos-Oreiro, MD, PhD, of the Department of Hematology at Gregorio Marañón Hospital in Madrid, Spain, and other colleagues. The goal of the study, according to the authors, was “to describe the global Spanish experience with CAR T-cell therapy in the commercial setting and compare these results with the historical treatment prior to the CAR T-cell therapy.”
The researchers retrospectively collected data from patients with LBCL who were treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel and 91 with tisagenlecleucel) and compared the results with a historical refractory population of patients (n=81).
The CAR-T cohort included all adult patients with aggressive B-cell lymphoma different from primary mediastinal LBCL who were registered in the GELTAMO/GETH-TC database of patients treated with CAR T-cell therapy in eight Spanish centers between February 2019 and July 2021. This cohort was compared with a historical population of relapsed/refractory diffuse LBCL patients from the GELTAMO-IPI study, treated in the pre-CAR T-cell therapy era (previous SOC).
The results showed superior efficacy for CAR-T therapy (for both drugs) over previous SOC, with longer progression-free survival ([PFS] median, 5.6 vs 4.6 months; P≤.001) and overall survival ([OS] median, 15 vs 8 months; P<.001), independently of other prognostic factors.
Within the CAR-T cohort, axicabtagene ciloleucel showed longer PFS (median, 7.3 vs 2.8 months, respectively; P=.027) and OS (58% vs 42% at 12 months, respectively; P=.048) compared to tisagenlecleucel.
However, axicabtagene ciloleucel was independently associated with a higher risk of severe cytokine release syndrome (CRS). The incidence of CRS was significantly higher in the patients treated with axicabtagene ciloleucel than those treated with tisagenlecleucel (90% vs 65%; P<.001). The incidence of severe CRS did not differ between the two CAR-T cohorts (8% vs 4%; P=.38).
A possible limitation noted by the authors is that the historical cohort received treatment before 2014, mainly with regimens based on chemotherapy and rituximab.
“Our results suggest that the efficacy of CAR T-cell therapy is superior to previous SOC in the real-world setting,” the authors concluded. “Furthermore, [axicabtagene ciloleucel] could be superior in efficacy to [tisagenlecleucel], although more toxic, in this group of refractory patients.”
Bastos-Oreiro M, Gutierrez A, Reguera J. Best treatment option for patients with refractory aggressive B-cell lymphoma in the CAR-T Cell era: real-world evidence from GELTAMO/GETH Spanish groups. Front Immunol. 2022; 13. Doi:10.3389/fimmu.2022.855730