Treatment with the CD19 chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) produced strong responses and low rates of severe adverse events (AEs) as second-line therapy among patients with high-risk or refractory follicular lymphoma (FL), according to findings presented at the 65th ASH Annual Meeting and Exposition.
These are the first findings reported for CD19 CAR-T therapy for this group of patients.
Franck Morschhauser, MD, PhD, the presenter and head of the lymphoma unit at Center Hospital University in Lille, France, said although the cohort was small, the high response rate was encouraging for use in these patients.
“There remains an unmet need for effective treatments in patients with relapsed or refractory FL, especially for those who relapse after one line of therapy and have high-risk features,” he said.
To be included in the phase II TRANSCEND FL trial, patients had to have disease progression within 24 months following treatment that had been received no longer than six months after the original diagnosis of FL, high tumor burden as defined by modified Groupe d’Etude des Lymphomes Folliculaires (mGELF) criteria, or both. All patients had received one prior combination of systemic therapy with an anti-CD20 antibody and alkylator.
Of the 23 patients who received liso-cel, the median age was 53 (range = 34-69), 74% had stage III or IV disease, and 35% had high-risk disease according to the Follicular Lymphoma International Prognostic Index. Sixty-five percent of patients had disease progression within 24 months from the start of their firstline therapy, 70% met the mGELF criteria, and 48% were double refractory to anti-CD20 antibody plus alkylator. Twenty-two percent had both high tumor burden and progressed within 24 months. Median on-study follow-up was 18.1 months.
Among those for whom efficacy was evaluable, the overall response rate and the complete response rate were both 95.7%. With a median follow-up of 16.8 months and 17.8 months, respectively, neither the median duration of response (DOR) nor the progression-free survival (PFS) was reached. The 12-month DOR rate was 89.8%, and 12-month PFS was 91.3%.
The drug showed rapid expansion. The median time to maximum transgene levels was 10 days, and persistence of liso-cel transgene was detected through month 12 in five of 19 patients.
The most common grade 3 or higher treatment- emergent AEs (TEAEs) were cytopenias, most frequently neutropenia, which was seen in 52% of patients. Cytokine release syndrome (CRS) was also seen in 52%, with none grade 3 or higher; the median time to CRS onset was six days, and median time to resolution was three days. Neurologic events occurred in 17% of patients, with median time to onset of 8.5 days and median time to resolution of 2.5 days. One TEAE death occurred as the result of disease progression due to grade 5 macrophage activation syndrome, researchers reported.
“We truly think,” Dr. Morschhauser said, “these data support liso-cel as a new potential treatment option, as soon as second line, in high-risk patients with FL.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Morschhauser F, Dahiya S, Palomba ML, et al. TRANSCEND FL: phase 2 study primary analysis of lisocabtagene maraleucel as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. Abstract 602. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 10, 2023; San Diego, California.
