Characterization of bridging therapies in clinical trials leading to FDA approval of CAR-T cell therapies.

Abstract

During the time of chimeric antigen receptor T-cell (CAR-T) manufacturing, bridging therapy is often used to control disease. Because it often involves systemic treatment, the bridging therapies can induce responses and/or adverse events. We sought to assess bridging therapies used in CAR-T trials in a cross-sectional study. We reviewed FDA drug labels and peer-reviewed registration trial reports (including supplemental data) to evaluate the characteristics of bridging therapy used in trials testing CAR-T therapies. We looked at which bridging therapies were used, whether multiple therapies were combined, the response rates, and the reported adverse events associated with bridging therapy. Of the 11 studies testing CAR-T therapies, 10 reported the bridging therapies that were used in the study. Of those that reported the types of bridging therapies (n = 10), the most commonly used bridging therapy was dexamethasone (10/10, 100%), rituximab (6/10, 60%), gemcitabine (5/10, 50%), and etoposide (5/10, 50%). Of the trials, one of 11 (9%) clearly reported whether patients had responses to bridging therapy, six of 11 (55%) vaguely reported responses, and four of 11 (36%) trials did not report or mention any response information regarding bridging therapy. Although patients are often refractory to first-line therapies, which share considerable overlap with bridging therapies, these therapies may induce responses. Despite this possibility, the reporting of bridging therapy combinations and their subsequent response rates and adverse event rates are highly variable. These findings highlight the need for greater transparency in the reporting of bridging therapy to more reliably assess the efficacy of CAR-T therapies.