In the phase II ZUMA-5 trial, axicabtagene ciloleucel led to responses in 92% of patients with indolent non-Hodgkin lymphoma treated with the cellular immunotherapy. These findings were reported by Caron Jacobson, MD, MMSc, and colleagues at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 700).

Axicabtagene ciloleucel is an autologous anti-CD16 chimeric antigen receptor (CAR) T-cell therapy approved for adult patients with relapsed/refractory large B-cell lymphoma previously treated with at least two regimens. ZUMA-5 tested this approach in relapsed indolent non-Hodgkin lymphoma after two or more previous lines of therapy.

Caron Jacobson, MD, MMSc

“In ZUMA-5, axicabtagene ciloleucel had considerable and durable clinical benefit in patients with indolent lymphoma, with high response rates and complete response rates,” said Dr. Jacobson, of Dana-Farber Cancer Institute. Responses were consistent among patients with high-risk features and, at a median follow-up of 17.5 months, were ongoing for 64% of patients with follicular lymphoma.

“We were very impressed with the magnitude of the responses, and also the durability [of responses],” said Dr. Jacobson. “This treatment has meaningfully affected high-risk patients with these diseases. I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas such as large B-cell lymphoma.”

About ZUMA-5

To test the efficacy of the therapy in indolent B-cell non-Hodgkin lymphoma, researchers administered axicabtagene ciloleucel to 146 patients, including 124 with follicular lymphoma and 22 with marginal zone lymphoma. After conditioning, they received axicabtagene ciloleucel at 2 × 10⁶ CAR+ cells/kg. The primary endpoint was objective response rate.

Axicabtagene ciloleucel was successfully manufactured for all enrolled patients and was delivered to the study site a median of 17 days after leukapheresis. The efficacy analysis was performed on 104 patients, including 84 with follicular lymphoma who had at least 12 months of follow-up and 20 with marginal zone lymphoma with at least 4 weeks of follow-up. The safety analysis included all 146 patients.

Objective Response Rate

As of March 12, 2020, median follow-up was 17.5 months for efficacy and 15.1 months for safety.

Overall, 92% of patients achieved an objective response to the treatment, and 76% achieved a complete response. By malignancy type, responses were seen in 94% of patients with follicular lymphoma and 85% with marginal zone lymphoma, with 80% and 60%, respectively, being complete responses. Responses deepened over time.

“With a median follow-up of 17.5 months, the estimated median duration of response was not reached for all patients, and 64% of those with follicular lymphoma had an ongoing response at data cutoff,” noted Dr. Jacobson. “The 12-month duration of response was 71.7%.” 

Median progression-free and overall survival were not reached. At 12 months, 73.7% of all patients were progression-free and 92.9% were alive. While overall survival was nearly identical between the two subtypes, progression-free survival was longer in the follicular lymphoma subset (77.5%) than the marginal zone lymphoma subset (45.1%).

Response rates were slightly higher, and rates of adverse events were slightly lower among patients with follicular lymphoma compared to those with marginal zone lymphoma. These trends should become better understood after data become available for more patients with marginal zone lymphoma, added Dr. Jacobson.

Safety Profile

Almost all patients experienced adverse events, with 86% experiencing grade ≥ 3 events, most commonly cytopenia (70%) and infection (16%). Grade ≥ 3 cytokine-release syndrome occurred in 7% of patients, and grade ≥ 3 neurologic events were seen in 19%. Three patients died, with one death related to axicabtagene ciloleucel: multisystem organ failure in the context of cytokine-release syndrome on day 7.

Grade 4 neurologic events were reported in three patients. Six patients had neurologic events of lesser severity, including memory impairment, attention disturbance, intermittent paresthesia, tremor, and facial paresthesia.

“Between [patients with] marginal zone and follicular lymphoma in this trial, [patients with] marginal zone [lymphoma] did have slightly worse toxicity and elevations in inflammatory markers,” Dr. Jaconson observed. Since these appeared similar to what is seen in aggressive lymphomas, she speculated, “The disease itself is probably what dictates the toxicity.”

“Based on the safety profile we observed, we plan to evaluate the potential for outpatient treatment with axicabtagene ciloleucel in indolent lymphoma,” she concluded.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.