For a review presented at ASCO 2021, Sonali M. Smith, MD, FASCO, Elwood V. Jensen Professor in Medicine and Chief of the Section of Hematology/Oncology at the University of Chicago, discussed the findings of two studies focused on the use of cellular therapy in relapsed/refractory follicular lymphoma (r/r FL).

“We know that FL has an excellent outcome, and the median survival approaches 20 years for the vast majority of patients,” Dr. Smith explained. “However, if we study outcome after relapse, we know that progression-free survival declines after each subsequent relapse, which is true even in the chemo-immunotherapy era. This is also correlated with a decrease in overall survival, which measures approximately 2 years by the time patients have gotten to their third line of intensive therapy. We also know that not all relapses are the same, and in fact, patients who have a relapse within 2 years of their initial chemo-immunotherapy have a 5-year survival of only 50%.”

The ZUMA-5 Trial
Dr. Smith noted that the first cellular therapy product was FDA approved in March 2021 for use in r/r FL following results of the ZUMA-5 trial, a single-arm study of axicabtagene ciloleucel with a primary endpoint of overall response rate (ORR). The ORR was 94%, among which 80% were complete responses. With a median follow-up of 18.5 months, there appears to be a plateau on the curve for both duration of response and progression-free survival, according to Dr. Smith.

The ELARA Trial
In the ELARA trial, which assessed tisagenlecleucel for r/r FL, 94 of 98 participants successfully received cell therapy, stressed Dr. Smith. Nearly one-fifth (18%) of patients received tisagenlecleucel in the outpatient setting, “which may have implications for how this product is used in the future,” added Dr. Smith. The primary endpoint for the study was complete response rate, which was 66%, and the overall response rate was 86%. With a follow-up of 10 months, it’s unclear if there will be a plateau on the curve for duration of response or for progression-free survival, as seen in the ZUMA-5 trial.

Patient Identification Is Key
“When it comes to deciding on cellular therapy, I think the most important aspect for my patient population is trying to figure out who should be considered for this type of intensive approach,” explained Dr. Smith. “If we look at the patient characteristics for [the ZUMA-5 and ELARA] trials, we see that these are overall very heavily pre-treated patients with a number of adverse prognostic features. They are generally young, with a median age of 57 or 60. But the vast majority had bulky disease. They also had four prior therapies in ELARA versus three in ZUMA-5. More than half had early progression of disease from their initial therapy, and the majority had refractory disease. When it comes to who should be considered, I think these patient characteristics should be kept in mind.”

Patient identification is key when considering cellular therapy for patients with follicular lymphoma, according to Dr. Smith, “and we need to refine this going forward, remembering that the vast majority of patients do well without aggressive therapies. If we can identify patients with adverse risk factors, I think that will be a very important step forward for that group of patients. At this time, it’s very difficult to say if there is a difference between [tisagenlecleucel and axicabtagene ciloleucel] in terms of efficacy or toxicity. There are some nuances and some differences, which we will have to see as time goes by. Despite ZUMA-5 having 18.5 months of follow-up and ELARA only has 10 months, in the big picture for FL, this is too short to make strong recommendations, and it’s really unclear if this is a cure. [Cellular therapy] is a very promising and appropriate option for some patients, but we certainly need more data.”