Tisagenlecleucel Demonstrates High Rates of Durable Responses in Relapsed/Refractory Follicular Lymphoma

The CAR T-cell product tisagenlecleucel (Kymriah) has been shown to elicit durable responses in adult patients with relapsed/refractory follicular lymphoma with a safety profile that compares favorably with other available products, according Stephen J. Schuster, MD.

Results from the phase 2 ELARA trial (NCT03568461), which were presented during the 2021 ASCO Annual Meeting, showed that at a median follow-up of 10.9 months, tisagenlecleucel elicited an objective response rate of 86.2% among 94 patients with relapsed/refractory follicular lymphoma who were evaluable for efficacy; this included a complete response rate of 66.0%. The median duration of response had not yet been reached, and the median time to next anti-lymphoma treatment had not yet been reached.

Moreover, the median progression-free survival (PFS; 95% CI, 12.1–not evaluable [NE]) and the median overall survival (95% CI, NE–NE) had not yet been reached. The 6-month PFS rate with the CAR T-cell therapy was 76% (95% CI, 65%-84%).

“When we are backed into a corner, meaning our existing therapies do not work, guess what? This [agent] works in those patients,” Schuster said. “The response rates are very high, but what is more important, is the durable responses [that we saw] in the pilot study was 60% at 5 years, and this looks like it will be the same.”

In an interview with OncLive^®, Schuster, director of 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, further discussed the clinical implications of the phase 2 ELARA trial evaluating tisagenlecleucel in patients with relapsed/refractory follicular lymphoma.

OncLive^®: What was the rationale for the ELARA study?

Schuster: My area of expertise is the treatment of lymphomas, or blood cancers that are derived from lymphocytes. A common [challenge faced] in our practice [has to do with our] patients who have follicular lymphoma, which is the second most common form of non-Hodgkin lymphoma. We care for a lot of these patients. Many patients do just fine without any therapy, or with our existing therapies. However, a small subset of these patients have problematic disease, and even though this is supposed to be a slow-moving disease which may or may not need treatment, they run through our existing options quickly. We needed something new for them.

What are the clinical implications of this study?

The study offers a new treatment approach for those patients [who need] more options. Not all patients with follicular lymphoma are going to need this approach, but some will. The study is important because this is a biologically-based treatment regimen, meaning that patients with prior responses to chemotherapy or those with diseases that have resistance mechanisms to 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. We had piloted this approach in a study that began in 2014, and we treated 14 patients who needed this kind of advanced therapy. Of those patients, approximately two-thirds are still in remission now, beyond 5 years.

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. If 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.

Other [approaches are] on the horizon for these patients, as well, but this is a nice option; it is capable, with a single treatment, to result in durable responses with acceptable toxicity. Earlier this year, the FDA had approved another form of CAR T-cell therapy for follicular lymphoma, axicabtagene ciloleucel [Yescarta; axi-cel], and it is very effective. However, I suspect we do not have the same number of years of follow-up with that [product], although it [appears to be] equally active. The treatment itself is a little more intensive [and it comes with] adverse effects [AEs] that require using the hospital. What is nice about tisagenlecleucel is that the toxicity is minimal, and it can be utilized in an outpatient setting.

Will this research change practice?

It will change clinical practice; it has changed mine. This study included 97 patients, and the pilot only had 14. However, the response rates and toxicities that have been observed are similar. I am optimistic that we are going to see excellent long-term results with this approach for some patients. Again, not all patients need it. It is [appropriate for] a subset of patients, but it should be reassuring to all patients that this therapy is available, should they ever need it.

Is there anything else that you would like to add?

Early in the development of the CAR T-cell approach, much of the work was done in patients with acute leukemias, such as acute lymphoblastic leukemia. The toxicities are vastly different in patients with leukemia than they are in those with lymphoma. Even among patients with lymphoma, the toxicities [experienced by] those with follicular lymphoma are different than the [ones reported by patients with] large cell lymphoma.

There is a [misconception] that this is an incredibly toxic therapy, but it is not, [when we] look at the data. 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.

Reference

1. Schuster SJ, Dickinson MJ, Dreyling MH, et al. Efficacy and safety of tisagenlecleucel in adult patients with relapsed/refractory follicular lymphoma: primary analysis of the phase 2 ELARA trial. J Clin Oncol. 2021;39(suppl 15):7508. doi:10.1200/JCO.2021.39.15_suppl.7508