Utilizing CAR T-Cell Therapy to Treat Patients With R/R Follicular Lymphoma

At the 2024 Lymphoma, Leukemia & Myeloma (LL&M) Congress in New York, New York, Daniel Landsburg, MD, University of Pennsylvania, Philadelphia, Pennsylvania, participated in a debate where he argued in favor of utilizing chimeric antigen receptor (CAR) T-cell therapy to treat patients with relapsed/refractory (R/R) follicular lymphoma (FL).

“In conclusion, the CAR-T products that we have available for follicular lymphoma are very effective and very safe. Maybe it's not so much which CAR-T product is better than the other, but how do we get our patients in better shape to be able to respond better to CAR T-cells regardless of the product that we use,” stated Dr Landsburg.

Transcript:

I'm Dan Landsberg, [an] associate professor of clinical medicine from the University of Pennsylvania. [I’m] here at LL&M 2024 and reviewing my presentation today about CAR T-cell for follicular lymphoma patients.

There are 3 commercially approved CAR T-cell products in the United States: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. [All] have very encouraging efficacy and safety data in the patients that have been treated with these products. They're all very similar, so I'll probably discuss them in bulk. They all have enrolled patients with R/R follicular lymphoma, mostly with 2 or more lines of prior therapy and have included patients with high-risk features such as early progression of disease or POD24, multiply refractory patients, patients with high risk [International Prognostic Scores] and other additional high-risk features.

These CAR-T products all had very encouraging responses. The overall response rates were close to 90% for most of the CAR-T products, and the complete response rates were in the 70% to 90% range, which was equally encouraging. The toxicity profiles were relatively low. There were low rates of high-grade cytokine release syndrome and high-grade immune effector cell-associated neurotoxicity syndrome (ICANS).

The long-term progression-free and overall survival data are encouraging, and it looks like long-term. At about 2 or 3 years out, we'll see about 50% or so rates of progression-free survival, and 70% to 80% rates of overall survival, which is very encouraging. These are patients treated on clinical trials.

We have a lack of real-world data for patients treated with commercial CAR-T, although it's emerging, and some data with axicabtagene ciloleucel would suggest that the outcomes both in terms of efficacy and safety are very similar in the real-world setting as compared to the clinical trial setting. [Despite] the fact than the real-world setting, we tend to treat higher-risk patients who are at risk for inferior outcomes.

Finally, while I feel that the products are very similar in terms of how effective they are, there are some features about the patients and their disease status going into CAR-T that may be more predictive of the response to therapy than which CAR-T product the patient's treated with. The first is total metabolic tumor volume. Multiple studies have suggested that a high amount of total metabolic tumor volume at the time the patient's enrolled on the CAR-T study can predict for inferior survival outcomes.

The second is use of recent, prior bendamustine. Obviously, a treatment we use in the early lines of therapy for patients with follicular lymphoma, but for those that have an early relapse or refractory disease after that therapy and receive CAR T-cell [therapy] soon thereafter, that's associated with inferior outcomes including survival rates as well as inferior CAR-T expansion and some other metrics related to that.

In conclusion, the CAR-T products that we have available for follicular lymphoma are very effective and very safe. Maybe it's not so much which CAR-T product is better than the other, but how do we get our patients in better shape to be able to respond better to CAR T-cells regardless of the product that we use.

Source:

Landsburg D. Debate: How to Prioritize Therapy for Patients with R/R FL: CAR-T. Presented at Lymphoma, Leukemia & Myeloma Congress; October 16-19, 2024. New York, NY.