Axi-Cel Shows Durable Responses, May Have Curative Potential in R/R Indolent Non-Hodgkin Lymphoma

Treatment with axicabtagene ciloceleucel (axi-cel; Yescarta) has not only maintained high response rates after 5 years in relapsed/refractory indolent non-Hodgkin lymphoma (NHL), but may have curative potential for a subset of patients with follicular lymphoma, according to Sattava S. Neelapu, MD.1

Updated safety and efficacy data from a 5-year analysis of the phase 2 ZUMA-5 trial (NCT03105336) were presented at the 2024 ASH Annual Meeting. At a median follow-up from leukapheresis of 64.6 months (range, 32.3-81.4), the study met its primary end point of overall response rate (ORR). All patients on the trial (n = 159) achieved an ORR of 90%, which included a complete response (CR) rate of 75% and a partial response (PR) rate of 14%. The ORRs were 94% vs 77% for patients in the follicular lymphoma (n = 127) and marginal zone lymphoma (MZL; n = 31) cohorts, respectively; the CR and PR rates for these cohorts were 79% vs 65% and 15% vs 13%, respectively.

“Importantly, we observed that within the follicular lymphoma cohort, there's a plateau in the lymphoma-specific PFS after the 2-year time point with only 2 relapses after the 30-month time point. To us, this indicates axi-cel is potentially curative for these patients,” Neelapu noted in an interview with OncLive® at the meeting.

In the interview, Neelapu provided an overview of the 5-year follow-up analysis of ZUMA-5, and shared updated efficacy and safety findings with axi-cel in indolent NHL.

Neelapu serves as a professor and the deputy department chair of the Department of Lymphoma/Myeloma, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center. He is also a member of the graduate faculty in the Graduate School of Biomedical Sciences Immunology Program at The University of Texas Health Science Center in Houston.

OncLive: What was the design of this 5-year follow-up analysis?

Neelapu: [We conducted a] 5-year follow-up analysis of the ZUMA-5 study, which is a phase 2, single-arm, multicenter study evaluating axi-cel in patients with relapsed/refractory indolent NHL. Axi-cel is an autologous anti-CD19 CAR T-cell therapy that's previously been approved for relapsed/refractory follicular lymphoma [by the FDA] in the third-line setting and beyond.2

After about 2 years of [additional] follow-up, we are now presenting the 5-year follow-up analysis of this study.1 To be eligible for this study, patients had to have either [relapsed/refractory] grade 1 to 3A follicular lymphoma or nodal or extranodal MZL.

In addition, they had to have at least 2 prior lines of therapy, including an anti-CD20 antibody and an alkylating agent. Following enrollment onto the study, the patients underwent leukapheresis. Once the [CAR T-cell] product had been generated, they received [lymphodepleting] chemotherapy with cyclophosphamide and fludarabine over 3 days. After 2 days of rest, they received a single infusion of axi-cel at a dose of 2 million CAR-positive cells/kg body weight. The primary end point of the study was ORR.

What efficacy findings were presented during the meeting?

A total of 159 patients were treated with axi-cel: 127 with follicular lymphoma and 31 with MZL. We now have a median follow-up of 64.6 months for all treated patients. For the follicular lymphoma [cohort, the median follow-up was] 65.7 months. For the MZL [cohort], the median follow-up was 55.8 months. The best ORR for all treated patients was 90.0%, and the CR rate was 75.0%. Within the follicular lymphoma cohort, we observed a higher CR rate of 79% vs 65% [in the] MZL [cohort].

We also performed an analysis to look at lymphoma-specific PFS. Within the follicular lymphoma cohort, we observed a plateau emerging after the 2-year time point. We had only 4 relapses after the 24-month time point, and only 2 relapses after the 30-month time point. The 60-month and the 5-year lymphoma-specific PFS rate was 64.0% [95% CI, 62.5-not evaluable (NE)], and the median overall survival [OS] had not been reached [95% CI, NE-NE]. The 5-year OS for follicular lymphoma was 83.4% [95% CI, 75.0%-89.1%].

In terms of the durability of responses, we observed the median duration of response was 60.4 months, the median time to next treatment had not been reached, and the median progression-free survival [PFS] was 62.2 months.

What should be known about the agent’s safety profile?

In terms of safety, since the 4-year analysis, we have not observed any new adverse [effects] related to axi-cel. A total of 46 patients died on the study; approximately half of them died due to progressive disease and half due to competing risks, such as secondary malignancies, cardiac events, infection, or other causes.

What is the clinical significance of these updated data?

Overall, these results indicate that axi-cel continues to be a highly effective therapeutic approach for patients with relapsed/refractory indolent NHL, with long-term durability of responses observed at 5 years [as well as] long-term survival.

References

1. Neelapu SS, Chavez JC, Sehgal AR, et al. 5-year follow-up analysis from ZUMA-5: A phase 2 trial of axicabtagene ciloleucel (axi-ce) in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Blood. 2024;144(suppl 1):864. doi: 10.1182/blood-2024-194627
2. FDA grants accelerated approval of axicabtagene ciloleucel for relapsed or refractory follicular lymphoma. News Release. FDA. Updated March 8, 2021. Accessed February 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-axicabtagene-ciloleucel-relapsed-or-refractory-follicular-lymphoma