Risk of infection in patients with hematological malignancies receiving CAR T-cell therapy: systematic review and meta-analysis

ABSTRACT

Background

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma. Underlying and treatment-related variables may contribute to the development of infectious complications.

Research design and methods

We conducted a systematic review and meta-analysis on the incidence of overall and severe (grade ≥3) infection in patients with hematological malignancies receiving CAR T-cells. Secondary outcomes included the specific rates of bacterial, viral and invasive fungal infection (IFI), and infection-related mortality. PubMed, Embase and Web of Science databases were searched from inception to 27 May 2022. Sensitivity analysis were performed according to the type of malignancy and study design (randomized clinical trials [RCTs] or observational studies).

Results

Forty-five studies (34 RCTs) comprising 3,591 patients were included. The pooled incidence rates of overall and severe infection were 33.8% (I² = 96.31%) and 16.2% (I² = 74.41%). The respiratory tract was the most common site of infection. Most events were bacterial or viral, whereas the occurrence of IFI was rare. The pooled attributable mortality was 1.8% (I² = 43.44%).

Conclusions

Infection is a frequent adverse event in patients receiving CAR T-cell therapy. Further research should address specific risk factors in this population.

KEYWORDS:

• CAR T-cell therapy
• infection
• incidence
• adverse event
• risk factor
• systematic review
• meta-analysis

Article highlights

• No previous meta-analyses analyzing the safety of CAR T-cell therapy in patients with hematological malignancies have been specifically focused on the incidence of and risk factors for infection in this at-risk population.

• In the present systematic review and meta-analysis (45 studies with 3,591 patients) the pooled incidence rates for overall and severe infection were high (33.8% and 16.2%, respectively), although moderate-to-high heterogeneity was observed for all outcomes.

• Upper respiratory tract infection, pneumonia and sepsis or bloodstream infection were the most commonly reported sites. The pooled estimate for infection-related mortality was low (1.8%).

• Most of the included studies did not provide granular data regarding the site of infection and causative agent, or whether the patient was receiving or not prophylaxis. The occurrence of IFI, however, was rarely reported.

• Prior HSCT, the number of previous lines of chemotherapy, the presence of baseline neutropenia, the severity of cytokine release syndrome and the requirement of anti-IL-6 agents and corticosteroids were identified in the few studies that assessed the risk factors for infection after CAR T-cell therapy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14787210.2022.2128762

Reviewer disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was funded by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, and co-funded by the European Union —European Social Fund, ‘Investing in your future.’ M.F.R. holds a research contract ‘Miguel Servet’ (CP18/00073) from the ISCIII. 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.