Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review (protocol).

Objective: To determine the efficacy and safety of CAR-T therapy in the treatment of patients with hematologic malignancies, in comparison with other current therapies.

Design: A living systematic review.

Methods: We will include randomized trials evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, best supportive care or any other intervention in patients with hematologic malignancies. Non-randomized primary studies will be searched in case we found no direct evidence from randomized controlled trials. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. Efficacy measures will include overall survival rate, overall response rate, complete response/remission (CR) rate, partial response/remission (PR) rate, relapse from CR, progression-free survival, and time from CAR-T infusion to transplantation. Safety measures will include serious adverse events, the incidence of cytokine release syndrome, graft-versus-host disease, neurotoxicity, and total adverse events. Quality of life will also be assessed. Meta-analyses will be carried out to summarize the results. We will apply the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available until there is solid evidence to respond to the review objective. We will resubmit it for publication every time the conclusions change or whenever there are substantial updates.