Identifying and managing CAR T-cell–mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team

ABSTRACT

Introduction

Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed.

Areas covered

The review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells.

Expert opinion

The development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk. The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually. The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.

KEYWORDS:

• CAR T therapy
• toxicity
• ICANS
• neurological toxicity
• biomarkers

Article highlights

• CAR T-cells is an innovative treatment for patients with refractory and relapsed hematologic malignancies.

• Prevention and treatment of CRS and neurotoxicity remain the main challenge.

• CAR T-cell therapy must be administered at centers with experience and established quality processes.

• The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on algorithms based on international guidelines and the internal clinical practice of the Center.

• It is urgent to identify biomarkers that could identify patients most at risk of developing CRS and neurotoxicity.

• The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually.

• An early start of cytokine blockade therapies could mitigate toxicity

• Cytokine release prophylaxis and a risk-adapted treatment are the approaches of the future to reduce the incidence of toxicity

This box summarizes key points contained in the article.

Declaration of interest

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

Reviewer disclosures

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

Additional information

Funding

This manuscript has not been funded.