Developing CAR T-Cell Therapies Offer Treatment Opportunities for Mantle Cell Lymphoma

With the approval of brexucabtagene autoleucel for the treatment of adults with mantle cell lymphoma (MCL), 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 American Society of Clinical Oncology (ASCO) 2021 Annual Conference.

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.

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.

Westin noted that 4 CAR T-cell therapies have been approved: tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel. Westin focused his presentation on brexucabtagene autoleucel and its approval for MCL.

According to Westin, MCL is approximately 3% to 6% of all non-Hodgkin lymphomas 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.

Clinical trials of aggressive therapies for MCL found a median progression-free survival (PFS) of 3 to 4 years with an aggressive regimen and a median overall survival (OS) from diagnosis of 85 months. At 5 years, the median OS is 66%.

Brexucabtagene autoleucel, formerly known as KTE-X19, is an anti-CD19 CAR T-cell therapy, Westin said in the presentation. The ZUMA-2 trial 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’s tyrosine kinase (BTK) inhibitor.

The trial found an overall response rate of 92% with the brexucabtagene autoleucel, which Westin said is remarkable. At a median follow-up of 17.5 months, 29 of 60 evaluable patients remain in ongoing responses, 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.

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

Finally, Westin said that it should only be administered 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 lengthy process, which can take 17 days before receiving the genetically modified immune cells.

REFERENCE

Westin J. FDA Approvals and Their Incorporation into Clinical Practice. Presented at: ASCO 2021 Annual Conference. June 4, 2021. Accessed June 7, 2021.