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. 2021 Jan 21;10(1):35.
doi: 10.1186/s13643-021-01588-7.

Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis

Komal Adeel #  1 , Nathan J Fergusson #  2   3 , Risa Shorr  4 , Harold Atkins  3   5   6 , Kevin A Hay  7   8   9
Affiliations

Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis

Komal Adeel et al. Syst Rev. .

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.

Keywords: Adverse events; B cell malignancies; CAR T cell; CD22; Chimeric antigen receptor; Complete response; Efficacy; Safety.

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Conflict of interest statement

KAH has received honorarium for speaking engagements from Jazz Pharmaceuticals and served on advisory boards for Kite/Gilead and Celgene/BMS. KAH is principal investigator on a BioCanRx grant (Ref #FY20/ES15) “Enabling a Phase I/II multicenter clinical trial of a novel single domain (sd)CD22 specific camelid chimeric antigen receptor (CAR) T-cell therapy”. HA is a co-investigator on an Ontario Institute for Cancer Research grant “Using real-world data and iterative economic evaluation to prioritize resource allocation for care and research in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia”. HA is also a member of a Council of Canadian Academies expert panel examining the legal, ethical, social, and policy challenges surrounding gene and engineered cell therapies.

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