Researchers reported long-lasting responses and no new safety concerns in patients with relapsed/refractory follicular lymphoma during the 2023 ASH Annual Meeting and Exposition.
Treatment with Kymriah (tisagenlecleucel) showed responses lasting more than three years in patients with relapsed/refractory follicular lymphoma, according to data from the phase 2 ELARA study that were presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition.
According to the Food and Drug Administration, Kymriah is a genetically modified autologous T-cell immunotherapy drug that targets a protein called CD19 in patients with relapsed/refractory follicular lymphoma.
A total of 81 responding patients (54%) maintained a response at the data cutoff. The likelihood of remaining in response 33 months following the first response was 63% for complete/partial response to treatment and 73% for complete response. Additionally, the likelihood of patients beginning a new treatment at 36 months following Kymriah was 35% in the efficacy evaluable population of 94 patients.
There were 98 total patients enrolled in the ELARA study and who underwent Kymriah manufacturing with the possibility of bridging therapy with chemotherapy.
A total of 97 patients underwent infusion with Kymriah and 94 were evaluated at the first efficacy assessment at month 3 after restaging and lymphodepletion (treatment to reduce the population of circulating lymphocytes) in patients who received bridging therapy. The study had a median follow-up of 40.6 months.
To be included in the study, patients were required to be 18 years of age or older with grade 1 to 3A relapsed/refractory follicular lymphoma. There also needed to be no evidence of histologic transformation/FL3B or prior treatment with anti-CD19 therapy or allogeneic hematopoietic stem cell transplant (a procedure when a patient receives healthy stem cells from a donor).
The study’s primary endpoint (the main result measured at the end of a study to see if treatment worked) was the complete response rate (no signs or symptoms of cancer because of its response to treatment).
The study’s key secondary endpoints included overall response rate (ORR; percentage of patients who show a partial or complete response to treatment), duration of response (DOR; length of time when a tumor responds to treatment without worsening) and progression-free survival (PFS; length of time during and after treatment when a patient’s cancer does not worsen).
Secondary endpoints from the study also included overall survival (OS; length of time from diagnosis or start of treatment when a patient is still alive) and safety.
Data from the study indicated that the median PFS was 37 months with a median follow-up of 30 months.
Additionally, the 36-month PFS rates in the overall population and those with a complete response to treatment were 53% versus 69%, respectively. The median OS among those treated with Kymriah was not reached, and the 36-month OS rate was 82%.
Researchers reported that neither the DOR nor the time to the next treatment was reached at a median follow-up of 41 months.
The median patient age was 57 years. Bulky disease was present in 64% of patients. Additionally, 63% of patients experienced progressive disease at 24 months following the first anti-CD20 monoclonal antibody-containing regimen.
There were 68% of patients who were double refractory to an anti-CD20 monoclonal antibody and alkylating agent. Patients also had several comorbidities at baseline, including cardiac disorders (16%), diabetes (10%) and renal insufficiency (poor function of the kidneys due to reduced blood flow; 8%).
It was reported that rates for PFS and OS at 36 months were consistent for patients who experienced progressive disease at 24 months and those without. Specifically, the 36-month PFS rate was 50% in those with progressive disease at 24 months and 59% in those without. The corresponding OS rates in each respective group were 83% and 80%.
Researchers also reported that high baseline levels of peripheral CD8-positive, naïve T cells correlated with long-lasting PFS and DOR.
“(These findings) were consistent with previously reported data from other very early studies in smaller datasets,” according to lead author Dr. Stephen J. Schuster, during a presentation on the findings. “Those patients who had a higher concentration of naïve T-cells, in particular CD8-positive naïve T-cells, were associated with having a prolonged PFS or DOR relative to those who had lower levels.”
Schuster — the director of the lymphoma program and lymphoma translational research, as well as a Robert and Margarita Louis-Dreyfus Professor in chronic lymphocytic leukemia and lymphoma clinical care and research at Penn Medicine — emphasized that those who had not experienced progressive disease at 24 months had a higher mean CAR transgene expansion and more durable persistence.
Responses and durations did not differ among the progressive disease at 24 months subgroups, despite expansion differences; CAR transgene persistence was reported up to 1,290 days.
Schuster indicated that there were no new findings regarding safety. The most common high-grade toxicities any time after infusion were neutropenia (low levels of white blood cells; 43%) and anemia (19%).
Frequent serious side effects included cytokine release syndrome (CRS; an aggressive response to immunotherapy drugs; 20%), pneumonia (11%), and febrile neutropenia (fever during a period of having low levels of white blood cells; 8%).
To date, a total of 18 patients died during the study, with eight dying due to progressive disease, nine due to side effects, and one to euthanasia. Side effects resulting in death included metastatic squamous cell carcinoma, encephalitis (brain inflammation), pneumonia, bladder transitional cell carcinoma, acute myeloid leukemia, infection, CRS, gastrointestinal hemorrhage and cardiac arrest.
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