Liso-Cel Response Rate Near 100% in Patients With Relapsed or Refractory Follicular Lymphoma

Two-year follow-up data from the phase 2 TRANSCEND FL study [NCT04245839] uphold previous reports of the high efficacy and safety of lisocabtagene maraleucel (liso-cel) as a treatment for patients with relapsed or refractory follicular lymphoma (FL).

The study was led by Jeremey S. Abramson, MD, of the Massachusetts General Hospital and associate professor of Medicine, Harvard Medical School, Boston, Massachusetts.

“Updated data from the TRANSCEND FL study continue to show high rates of durable remission for third-line or later FL patients treated with liso-cel. Specifically, among [103] multiple relapsed patients with a median of three prior lines of therapy, two out of three of whom were refractory to their prior treatment, the complete response [CR] rate was a remarkable 94% [(95% CI, 87.8-97.8)],” Dr. Abramson told Blood Cancers Today. “This is the highest CR rate ever reported in such a high-risk population of relapsed FL.”

Among  patients who received 100 × 10⁶ CAR T cells of liso-cel in the third line setting and 23 in the second line, the objective response rates were 97.1% (95% CI, 91.7-99.4) and 95.7% (95% CI, 78.1-99.9), respectively. The median follow-up was 30.0 months (0.3-39.6) in third line patients and 29.5 months (95% CI, 1.0-38.2) in second line patients. The CR rates in patients treated in the second line setting was 95.7% (95% CI, 78.1-99.9).

“Importantly, with extended follow up, the responses are durable with three out of four patients remaining in response at two years. A smaller cohort of patients with high-risk features treated in second line with liso-cel also showed ongoing deep and durable remissions,” explained Dr. Abramson.

The data show a 24-month duration of response (DOR) of 74.6% (95% CI,64.8-82.1) among patients treated in the third line setting and 86.4% (63.4-95.4) for patients treated in the second line.

Regarding survival, patients treated with liso-cel in the third line had a 72.5% (62.7-80.1) progression-free survival (PFS) and an 88.2% (95% CI, 80.1-93.1) overall survival (OS). In the same cohort, the probability of time to next treatment (TTNT) was 80.1% (70.8-86.7) and the probability of time from randomization to objective tumor progression (PFS2) was 76.6% (95% CI, 57.7-87.9). Patients in the second line cohort showed a PFS of 82.6% (95% CI, 60.1-93.1) and an OS rate of 95.7% (95% CI, 72.9-99.4), with a 91.3% (95% CI, 69.5-97.8) probability of TTNT and 91.1% (95% Ci, 68.8-97.7) probability of PFS2.

Up to month 30, the endurance of the liso-cel transgenes was observed in 25% of third line patients and 17% of second line patients.

The median follow-up for safety in the TRANSCEND FL study was 18.9 months. Dr. Abramson stated that “liso-cel was very well tolerated with low rates of cytokine release syndrome [CRS], ICANS and prolonged cytopenia.”

There was a 1% incidence of grade ≥3 CRS in the study and no grade 4/5 events. Two percent of patients experienced grade ≥3 neurological events (NEs) and 22% had prolonged cytopenia. Five patients presented with secondary malignancies; of them, seven were treated in the third line setting and two in the second line. Notably, none of the secondary malignancies were T cell-related.

Of the patients who underwent leukapheresis, 16 died during the study. In the outpatient treatment setting (n=14), there were no incidences of grade ≥3 CRS, NEs, or prolonged cytopenia at the time of data cutoff.

“These data all support liso-cel is a remarkably effective and well-tolerated treatment for relapsed/refractory FL capable of producing deep and durable complete remissions with a single infusion of an extremely well-tolerated CAR T-cell product,” Dr. Abramson stated.

REFERENCE:

Nastoupil L, Dahiya S, Palomba M, et al. Lisocabtagene maraleucel (liso-cel) in patients (pts) with relapsed or refractory (r/r) follicular lymphoma (fl): transcend fl 2-year follow-up. Presented at: 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 4387.