Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma

ABSTRACT

Introduction

Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was recently approved for relapsed or refractory follicular lymphoma following progression on two or more lines of therapy including an anti-CD20 monoclonal antibody with an alkylating agent, providing a therapeutic breakthrough in a subset of indolent non-Hodgkin lymphoma associated with poor clinical outcomes.

Areas covered

In this article, we outline the drug profile of axicabtagene ciloleucel in comparison to currently approved agents and other CAR T-cell and T-cell redirecting therapies under investigation for the treatment of relapsed or refractory follicular lymphoma. We also review the efficacy, safety, and pharmacokinetic data from the ZUMA-5 phase II trial, which forms the basis of the recent approval of axicabtagene ciloleucel.

Expert opinion

Axicabtagene ciloleucel is the first cellular therapy approved for relapsed or refractory follicular lymphoma, demonstrating high rates of durable responses and a manageable toxicity profile in heavily pre-treated patients.

KEYWORDS:

• Follicular lymphoma
• axicabtagene ciloleucel
• CAR T-cell
• bispecific antibody
• indolent non-Hodgkin’s lymphoma
• treatment
• cellular therapy

Article highlights

• FL is considered incurable and advanced disease is marked by frequent relapses.

• For patients with relapsed or refractory FL, especially those who have undergone multiple lines of therapy, long-term remissions are rare and ongoing treatment is required.

• Axicabtagene ciloleucel is a second generation autologous anti-CD19 CAR T-cell that received accelerated approval in March 2021 for adult patients with relapsed or refractory FL who have failed at least 2 prior lines of therapy.

• Salvage with axicabtagene ciloleucel in patients with FL after failure of two or more lines of previous therapy is associated with high rates of complete response and durable remissions, lasting a median of greater than 3 years.

• Grade ≥3 treatment complications including CRS and ICANS were observed in 6% and 15% of patients, respectively.

• Pending approval, bispecific T-cell redirectors will likely become complementary in managing patients with relapsed or refractory FL.

Further reading

Ghobadi A, DiPersio JF. Gene and Cellular Immunotherapy for Cancer. Springer Nature, 2022.

Neelapu SS, Chavez JC, Sehgal AR. Long-term follow-up analysis of ZUMA-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (NHL). Blood. 2021 (138).

Ghobadi A, Bartlett NL. CD3xCD20 bispecific T-cell redirectors for relapsed or refractory B-cell lymphoma. Lancet. 25 Sep 2021;398(10306):1109-1110.

Declaration of interest

A. Ghobadi has received research support from Kite Pharma-Gilead and Amgen. Advisory Board Member/Consultant for Kite Pharma-Gilead, Amgen, Celgene, EUSA, Atara, CRISPR Therapeutics, and Wugen.

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

A reviewer on this manuscript has received honoraria/fees from Kite Pharma, BMS, Janssen, and Novartis related to CAR T-cell therapy.

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

Additional information

Funding

This paper received no funding.