The burden of SARS-CoV-2 in patients receiving chimeric antigen receptor T cell immunotherapy: everything to lose

ABSTRACT

Introduction

Chimeric antigen receptor T (CAR-T) cell immunotherapy has revolutionized the prognosis of refractory or relapsed B-cell malignancies. CAR-T cell recipients have immunosuppression generated by B-cell aplasia, leading to a higher susceptibility to respiratory virus infections and poor response to vaccination.

Areas covered

This review focuses on the challenge posed by B-cell targeted immunotherapies: managing long-lasting B-cell impairment during the successive surges of a deadly viral pandemic. We restricted this report to data regarding vaccine efficacy in CAR-T cell recipients, outcomes after developing COVID-19 and specificities of treatment management. We searched in MEDLINE database to identify relevant studies until 31 March 2022.

Expert opinion

Among available observational studies, the pooled mortality rate reached 40% in CAR-T cell recipients infected by SARS-CoV-2. Additionally, vaccine responses seem to be widely impaired in recipients (seroconversion 20%, T-cell response 50%). In this setting of B-cell depletion, passive immunotherapy is the backbone of treatment. Convalescent plasma therapy has proven to be a highly effective curative treatment with rare adverse events. Neutralizing monoclonal antibodies could be used as pre-exposure prophylaxis or early treatment but their neutralizing activity is constantly challenged by new variants. In order to reduce viral replication, direct-acting antiviral drugs should be considered.

KEYWORDS:

• CAR-T cell therapy
• SARS-CoV-2
• Covid-19
• vaccine
• B-cell aplasia
• outcomes
• convalescent plasma
• antiviral treatment

Article highlights

• CAR-T cell recipients have B-cell aplasia or hypogammaglobulinemia and a loss of the T-cell repertoire diversity, resulting in viral susceptibility.

• Based on small sample-size observational studies, CAR-T cell recipients have one of the highest mortality rates due to SARS-CoV-2 infection among all lymphodepleted patients.

• CAR-T cell recipients have a low seroconversion rate after COVID-19 mRNA vaccine, even after booster doses.

• Studies assessing COVID-19 therapies in lymphodepleted patients are scarce.

• Convalescent plasma appears to be a tailored treatment to overcome B-cell aplasia in CAR-T cell recipients.

Declaration of interest

P Sesques discloses honoraria, and advisory/consultancy BMS, Novartis, Kite/Gilead and Chugai. F Wallet discloses personal fees from Kite/Gilead and Novartis. E Bachy discloses honoraria and consultancy from Gilead, Novartis, Roche, Amgen, Janssen, Sanofi, and Abbvie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.