A review of chimeric antigen receptor T-cells in lymphoma

ABSTRACT

Introduction: Immunotherapy has revolutionized the treatment of cancer. Antibodies, antibody drug conjugates, and bispecific antibodies have improved outcomes in various cancers especially lymphomas. Chimeric antigen receptor T cell (CAR-T) is a step forward in the immunotherapy paradigm for the treatment of Lymphomas. Recently, two CAR-T products, Tisagenlecleucel and Axicabtagene ciloleucel, were approved by the US FDA. While it is exciting to have such novel treatment available, the challenges of production, administration, related toxicity, and cost remain. Specific toxicities related to CAR-T like Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) could be fatal and need close monitoring and prompt treatment to avoid mortality and improve efficacy of the treatment.

Areas covered: In this article, the authors discuss receptor constructs, administration, toxicities, efficacy and reimbursement of CAR-T treatment.

Expert opinion: Since approval of CAR-T treatment, cost of therapy and reimbursement have been a big challenge in implementation of CAR-T. This has triggered cost-effective analysis and nationwide discussions about the reimbursement process of such treatment. In spite of these challenges, CAR-T treatment is a huge step forward with a very bright future. Novel CAR-T targeting a variety of antigens in different cancers seems promising in near future.

KEYWORDS:

• CAR-T
• cytokine release syndrome
• lymphoma
• adoptive t-cell therapy
• chimeric antigen receptor T-cell
• immune effector cell associated neurotoxicity syndrome

Article highlights

• The most impressive response to therapy is seen in DLBCL with CR rates exceeding 50% but response to therapy is documented in tFL, CLL, MCL, and HL as well.

• Substantial evidence supports use of a conditioning regimen prior to CAR-T infusion based on improved CAR-T persistence and improved response.

• Increased disease burden is associated with increased toxicity so tumor debulking prior to therapy with CAR-T is a reasonable approach to minimize toxicities.

• Combinatorial Cyclophosphamide/Fludarabine appears to be an effective pretreatment conditioning regimen with improved toxicity

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 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

A reviewer on this manuscript has received honoraria and consulted for Kite/Gilead, Novartis and Juno/Celgene. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.