Abstract
Background
Chimeric antigen receptor (CAR) T cell therapy has had great success in treating patients with relapsed or refractory B cell malignancies, with CD19-targeting therapies now approved in many countries. However, a subset of patients fails to respond or relapse after CD19 CAR T cell therapy, in part due to antigen loss, which has prompted the search for alternative antigen targets. CD22 is another antigen found on the surface of B cells. CARs targeting CD22 alone or in combination with other antigens have been investigated in several pre-clinical and clinical trials.
Given the heterogeneity and small size of CAR T cell therapy clinical trials, systematic reviews are needed to evaluate their efficacy and safety. Here, we propose a systematic review of CAR T cell therapies targeting CD22, alone or in combination with other antigen targets, in B cell malignancies.
Methods
We will perform a systematic search of EMBASE, MEDLINE, Web of Science, Cochrane Register of Controlled Trials, clinicaltrials.gov, and the International Clinical Trials Registry Platform. Ongoing and completed clinical trials will be identified and cataloged. Interventional studies investigating CD22 CAR T cells, including various multi-antigen targeting approaches, in patients with relapsed or refractory B cell malignancies will be eligible for inclusion. Only full-text articles, conference abstracts, letters, and case reports will be considered. Our primary outcome will be a complete response, defined as absence of detectable cancer. Secondary outcomes will include adverse events, overall response, minimal residual disease, and relapse, among others. Quality assessment will be performed using a modified Institute of Health Economics tool designed for interventional single-arm studies. We will report a narrative synthesis of clinical studies, presented in tabular format. If appropriate, a meta-analysis will be performed using a random effects model to synthesize results.
Discussion
The results of the proposed review will help inform clinicians, patients, and other stakeholders of the risks and benefits of CD22 CAR T cell therapies. It will identify gaps or inconsistencies in outcome reporting and help to guide future clinical trials investigating CAR T cells.
Systematic review registration
PROSPERO registration number: CRD42020193027
Guidance for Developing Phase II Cell Therapy Trial Proposals for Consideration by the Blood and Marrow Transplant Clinical Trials Network