FDA-Approved CAR T-Cell Therapies Offer New Treatment Opportunities for Mantle Cell Lymphoma

With the accelerated approval of brexucabtagene autoleucel (Tecartus; Kite Pharma, Gilead Sciences Inc) for the treatment of adults with mantle cell lymphoma (MCL),¹ chimeric antigen receptor (CAR) T-cell therapies have become key treatments for various cancers, despite their high cost and other challenges, according to a presentation at the 2021 American Society of Clinical Oncology Annual Meeting.²

CAR T-cell therapies are genetically modified immune cells, according to presenter Jason Westin, MD, MS, FACP, leader of the diffuse large B-cell lymphoma research team at the University of Texas MD Anderson Cancer Center. He said CAR T cells are usually autologous, although a new allogenic generation is in development.²

Westin noted that 4 CAR T-cell therapies have been approved: tisagenlecleucel (Kymriah; Novartis), axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead Sciences Inc), lisocabtagene maraleucel (Breyanzi; Juno Therapeutics), and brexucabtagene autoleucel. However, Westin focused his presentation on brexucabtagene autoleucel and its approval for MCL.²

MCL occurs in approximately 6% of all non-Hodgkin lymphomas in the United States³ and is typically defined by 11;14 translocation. It has both good and bad features, Westin said, including the fact that it is frequently sensitive to many therapeutics, but often relapses and is considered incurable. Common therapies include platinum-based chemotherapies and very intensive approaches.²

In the MCL treatment space, Westin said historic study results prior to CAR T-cell therapy were abysmal. New outcomes with CAR T cells, however, show a routine 40% to 50% of patients long term who do not relapse.²

Brexucabtagene autoleucel, formerly known as KTE-X19, is an anti-CD19 CAR T-cell therapy, Westin said in the presentation. The ZUMA-2 trial (NCT02601313) investigated its use in adults with MCL who have relapsed or are refractory to between 1 and 5 prior therapies, including anthracycline or bendamustine, a CD20 antibody, and a Bruton tyrosine kinase (BTK) inhibitor.^2,4

The trial found an overall response rate of 92% for brexucabtagene autoleucel, which Westin said is remarkable. At a median follow-up of 17.5 months, 29 or 60 evaluable patients remained in ongoing responses at data cutoff, and 28 of 40 patients who achieved complete response remain in response. Notably, the median duration of response, progression-free survival, and OS have not yet been reached with a median follow-up of 17.5 months.^2,4

Westin added that adverse effects are significant, although they tend to diminish in incidence and severity the further out patients get from administration of brexucabtagene autoleucel.² Notably, 91% of patients had any grade of cytokine release syndrome, although just 15% had grade 3 or higher.⁴

Finally, Westin said brexucabtagene autoleucel should be administered only in a CAR T-cell center rather than a typical oncology clinic. He said physicians should recommend patients as early as possible in order to get an appointment, receive insurance approval, and begin the long process, which can take 17 days before the genetically modified immune cells are received.²

REFERENCES

1. FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. News release. [news release]FDA. July 27, 2020; FDA. AccesseeAccessed July 16, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-mantle-cell-lymphoma

2. Westin J. FDA Approvals approvals and Their theiriIncorporation into Clinical clinical Practicepractice. Presented at: 2021 ASCO 2021 Annual Meeting. Conference. June 4, 2021. Accessed June 7, 2021.

3. Mantle Cell cell Lymphomalymphoma. Lymphoma Research Foundation. Accessed July 16, 2021. https://lymphoma.org/aboutlymphoma/nhl/mcl/

4. New data for Tecartus demonstrate durable responses at one year follow-up in relapsed or refractory mantle cell lymphoma. News release. Kite and Gilead Sciences Inc. [news release]. December 5, 2020; Kite and Gilead Sciences Inc. Accessed July 16, 2021. https://www.kitepharma.com/news/press-releases/2020/12/new-data-for-tecartustm-demonstrate-durable-responses-at-one-year-follow-up-in-relapsed-or-refractory-mantle-cell-lymphoma