At the 2024 American Society of Hematology Annual Meeting, Dr. Sattva S. Neelapu sat down with CURE® to discuss the phase 2 ZUMA-5 trial which evaluated the CAR-T cell therapy Yescarta (axicabtagene ciloleucel) in patients with relapsed/refractory indolent non-Hodgkin lymphoma, including follicular lymphoma. According to Neelapu, the CAR-T cell therapy resulted in deep and durable responses for patients.
“Based on this five-year analysis… [this] CAR-T cell therapy is potentially curative for patients with relapsed/refractory follicular lymphoma,” he emphasized.
Furthermore, in the interview, Neelapu delved into insights on the quality-of-life patients being treated with this therapy can expect in the long term, as well as long-term challenges associated with the therapy.
Neelapu is a professor and deputy department chair in the Department of Lymphoma/Myeloma, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, in Houston, as well as a member of Graduate Faculty, Immunology Program, Graduate School of Biomedical Sciences, at The University of Texas Health Science Center, also located in Houston.
CURE: How does the durability of response with Yescarta compare with traditional therapies for follicular lymphoma?
Neelapu: Compared with other therapies that are currently available for relapsed/refractory follicular lymphoma — including therapies such as [Rituxan (rituximab)] and [Revlimid (lenalidomide)], or [Rituxan] with chemotherapy such as [Treanda (bendamustine)] or other chemotherapy regimens, [as well as] targeted therapies such as [Tazverik (tazmetostat)] or BTK inhibitors such [Brukinsa (zanubrutinib)] — we saw that the durability of response is much, much longer with the CAR-T cell therapy Yescarta. In fact, with most of the therapies, the median duration of response is about one to one and a half years in the third-line setting and beyond for follicular lymphoma, whereas here we are seeing a five-year median duration of response, which I think is remarkable.
Most of these therapies are not considered curative for follicular lymphoma, but based on this five-year analysis and the plateau in the lymphoma-specific progression-free survival [PFS], CAR-T cell therapy is potentially curative for relapsed/refractory follicular lymphoma. Even compared with T cell engagers, which are more recently approved for follicular lymphoma, such as mosunetuzumab which has a median duration of response and a PFS in the two-year range, whereas now we are seeing five-year durability of responses with CAR-T cell therapy.
How does Yescarta impact the quality of life of patients with relapsed/refractory follicular lymphoma in the long term?
One appealing thing about CAR-T cell therapy is it's a one-and-done therapy. Patients receive a one-time infusion. The adverse effects which might develop, such a cytokine release syndrome and neurological toxicities — if any — tend to occur within the first two weeks after the infusion, during which time the patients are closely monitored.
Usually by the one-month time point, or with the first two to three months, their quality of life returns back to the baseline, if not even better than baseline, because now they don't have disease-related symptoms.
What are the potential challenges and limitations of CAR-T cell therapy and how are they being addressed in ongoing research?
One potential limitation of CAR-T cell therapy in general is that it is available only at [a] limited number of centers. Currently, there are approximately 125 centers that administer CAR-T cell therapy. [Therefore], it does require patients to travel to a CAR-T center to be able to receive this therapy, and they generally need to stay in the area for about a five-week period, along with the caregiver, preferably. Usually, part of the stay could be in the hospital, but during the rest of the time, they're monitored in the outpatient unit.
Glossary:
CAR T-cell therapy: a type of cancer immunotherapy where a patient's own T cells are genetically engineered in a lab, allowing them to specifically recognize and kill cancer cells when reinfused back into the patient.
Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.
Cytokine release syndrome: a large, rapid release of cytokines from immune cells into the blood that may result from immunotherapy. Symptoms may include nausea, fever, rash, headache, low blood pressure, rapid heartbeat and trouble breathing.
That's one limitation, and the other limitation is because this is a patient-specific therapy, cost is definitely a limitation. Although it's an FDA-approved indication, currently, so it is covered by most insurances, as well as Medicare and Medicaid.
Transcript was edited for clarity and conciseness.
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.
