Study Examines Axi-Cel Use for Follicular Lymphoma Management

New research offers insights into the use of axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy (CAR T), for management of follicular lymphoma (FL).

Writing in Cancer Management and Research, authors described axi-cel and other CAR T-cell therapies as “a welcome addition to the treatment armamentarium of FL, yielding impressive responses in heavily pretreated cases and with relatively well-tolerated side effects.”

“Future efforts should focus on making this treatment available to all patients for whom this treatment is indicated, as its current cost makes it prohibitive and unaffordable in developing countries,” they added.

Even in the presence of high-risk features like early relapse, heavily pretreated patients, and bulky disease, axi-cel has shown high efficacy in relapsed/refractory (R/R) FL. FL is the second most common lymphoma in the Western hemisphere and accounts for around one-third of all non-Hodgkin lymphomas.

Axi-cel was first approved by the FDA in March 2021 based on results of the ZUMA-5 trial. It has 3 main components: an extracellular portion with the single chain variable fragment antibody domain that targets CD19, a transmembrane or hinge portion, and an intracellular (signaling) portion comprising a CD3zeta activation domain coupled with the costimulatory molecule, CD28 (CD19-CD28-CD3zeta), the authors wrote.

The ZUMA-5 trial included 124 patients with FL, 148 patients with R/R indolent non-Hodgkin lymphoma (NHL), and 24 patients with indolent NHL (NHL), all treated with axi-cel.

Of those with FL, 52% had bulky disease, 85% had stage IV disease, and 63% were heavily pretreated with more than 3 lines of therapy. Another 55% had a progression of disease within 24 months of receiving frontline chemotherapy, while 24% received and failed previous autologous stem cell transplant.

“With a median follow up for FL patients of 30.9 months, the ORR [overall response rate] following axi-cel for patients with FL was high, at 92%, with 76% of the patients achieving complete remission,” the authors wrote. “High response rates translated into durable responses, with a duration of response in FL patients of 38.6 months, and 57% of eligible patients were in ongoing response at data cut-off,” they added.

They went on to compare the ZUMA-5 findings with the ELARA study, which assessed the role of tisa-cel, another CAR T-cell therapy, in R/R FL. Matched adjusted indirect comparisons showed similar ORRs, complete remission rates, and progression-free survival.

Tisa-cel was also associated with a better safety profile than axi-cel. “While such comparison has inherent biases, it suggests that using either of those CAR T products could possibly lead to similar outcomes,” the researchers said.

To the authors’ knowledge, no study has evaluated the prognostic predictors of toxicities in patients with FL who have received CAR T-cell therapy, meaning the selection of tisa-cel vs axi-cel as the preferred therapy is up to each physician’s discretion.

However, because of its high efficacy and potential life-threatening toxicities, it’s imperative to determine which patients are best suited to axi-cel therapy. Potential factors that could affect eligibility include comorbidities, logistics, and need of caregiver.

Axi-cel is also associated with higher rates of cytokine release syndrome and neurologic events, but has a faster manufacturing time, although longer follow-up is needed to confirm these findings and assess survival. Outcomes of patients receiving check point inhibitors following CAR T-cell therapy remain unknown.

Overall “in the third-line setting, the treatment patterns for R/R FL are highly heterogenous, reflecting the lack of a definitive standard approach,” the researchers wrote.

Reference

Mohty R, Kharfan-Dabaja MA, Chavez JC. Axicabtagene ciloleucel in the management of follicular lymphoma: current perspectives on clinical utility, patient selection and reported outcomes. Cancer Manag Res. Published online April 19, 2023. doi:10.2147/CMAR.S368588