Efficacy of Tisagenlecluecel Yields Viable Option in Treating Follicular Lymphoma

Tisagenlecleucel is a CAR T-cell therapy approved to treat follicular lymphoma that has minimal toxicity and is safe in the outpatient setting.

Tisagenlecleucel (Kymriah) has induced durable outcomes in treating adult patients with relapsed/refractory follicular lymphoma and is comparable to other available products in terms of safety, said Stephen J. Schuster, MD.

Tisagenlecleucel resulted in an objective response rate (ORR) of 86.2% at the median follow-up at 10.9 months, according to results from the phase 2 ELARA trial (NCT03568461), which were presented during the 2021 ASCO Annual Meeting. In total, 94 patients with relapsed/refractory follicular lymphoma were included in the trial, of whom 66.0% experienced a complete response rate.

The study has yet to determine median duration of response, as well as median time to next anti-lymphoma treatment. In addition, neither the median progression-free survival (PFS; 95% CI, 12.1–not evaluable [NE]) nor the median overall survival (OS; 95% CI, NE–NE) has been reached, however, the 6-month PFS was 76% (95% CI, 65%-84%) with the CAR T-cell therapy.

“These findings offer hope in the sense that if a patient needs therapy, and existing therapies are inadequate—if they go through a couple of therapies, such as anti-CD20–based therapies like rituximab [Rituxan] with or without chemotherapy, and it is not working—this is an alternative that will work in those situations where [those] therapies have failed,” said Schuster, director of the Lymphoma Program and lymphoma translational research at Penn Medicine, and Robert and Margarita Louis-Dreyfus Professor in chronic lymphocytic leukemia and lymphoma clinical care and research, in an interview with OncLive®, Oncology Nursing News®'’s sister publication.

“It offers hope even for the patients who do not need it, should they ever get into that situation. We already have 5 years of follow-up, and this study has just under 1 year of median follow-up, as of the last data cutoff, which was September 2020,” he added.

Schuster noted that throughout his experience treating lymphomas, or lymphoma-related blood cancers, follicular lymphoma—the second most common form of non-Hodgkin lymphoma—has presented itself as a particular challenge. There is a high volume of patients with follicular lymphoma, and while a large number of them are fine without therapy, or respond well to existing therapies, there remains a subset of patients with problematic disease or whose disease moves at a much faster pace than existing therapies can treat.

“We needed something new for them,” he said.

This study marked a new turning point in follicular lymphoma treatment because tisagenlecleucelis, a biologically-based treatment regimen, signified that even patients whose diseases have failed to respond or have demonstrated resistance mechanism to previous lines of chemotherapy, will still respond.

“Immunotherapies, like this form of cellular immunotherapy, are agnostic. All the things which bode for failure of response to conventional agents are irrelevant when we are using this approach,” he explained.

The research team had first piloted this approach in 2014, with a study that included 14 patients who required this type of advanced therapy. More than 5 years later, approximately two-thirds of those patients are still in remission.

In addition, the current advances in CAR T-cell approaches are crucial because much of the early CAR T-cell development was concerned with the associated adverse events (AEs) when treating leukemias versus lymphomas. Understanding which toxicities are associated with different malignancies are a crucial component in supporting patients undergoing CAR T-cell therapy, Schuster said. Even within a population of patients with lymphoma, the toxicities can vary greatly between patients with follicular and large cell lymphoma, he noted.

“There is a [misconception] that this is an incredibly toxic therapy, but it is not, [when we] look at the data,” Schuster concluded. “If we look at serious episodes of AEs that are unique to CAR T-cell therapy, for example, cytokine release syndrome [CRS], no grade 3 or higher CRS [was reported with the product]. In acute leukemias and large cell lymphomas, a significant percentage of patients, particularly in leukemia, will experience grade 3 or higher CRS. [This is] very exciting in that the safety signal is good.”

The toxicity associated with tisagenlecluecel has been reported to be minimal. The drug is therefore considered safe to be used in the outpatient setting.

Other similar therapies are also in the pipeline for this population. In early 2021, the FDA approved axicabtagene ciloleucel (axi-cel; Yescarta), another form of CAR T-cell therapy, to treat follicular lymphoma. Schuster acknowledged that the drug seems to be comparable in efficacy, although he suspects we do not currently have the same number of years of follow-up with that product. Axicabtagene is known to be a slightly more intense treatment and is associated with higher grade AEs. Both drugs seem to be equally active, he said.

A version of this article was published on OncLive as “Tisagenlecleucel Demonstrates High Rates of Durable Responses in Relapsed/Refractory Follicular Lymphoma”