FDA Grant Priority Review to Liso-cel In Relapsed/Refractory Large B-cell Lymphoma

The FDA has granted Priority Review to the Biologics License Application (BLA) for lisocabtagene maraleucel (liso-cel) for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma, after at least 2 prior therapies. The Prescription Drug User Fee Act (PDUFA) goal date of August 17, 2020, has been set by the FDA, Bristol Myers Squibb Company announced in a press release.¹

TheBLA is supported by the safety and efficacy results of the phase I TRANSCEND NHL 001trial, which is evaluating treatment with liso-cel in this patient population. In December 2019, it was announced that the study met its primary and secondary end points.

There were 256 patients who were evaluable for efficacy out of 344 total patients who underwent leukapheresis. The overall response rate (ORR) observed was 73% (95% CI, 67%-78%), and of the 187 patients who responded to liso-cel treatment, 136 (53%) achieved a complete response (CR; 95% CI, 47%-59%). The responses were similar across all patient subgroups. The media duration of response (DOR) was not reached (NR) in the overall population of patients (95% CI, 8.6 months-NR), at a median follow-up of 12 months (95% CI, 11.2-16.7).²

In terms of survival, median progression-free survival (PFS) was 6.8 months (95% CI, 3.3-14.1), and median overall survival (OS) was 21.1 months (95% CI, 13.3-NR). Among the patients who achieved a CR, the median PFS and OS were NR, with rates at 12 months being 65.1% and 85.5%, respectively.

The safety analysis showed that 79% of patients experienced grade ≥3 treatment-emergent adverse events (TEAE), which included neutropenia (60%) anemia (38%), and thrombocytopenia (27%). Cytokine release syndrome of any grade occurred in 42% of patients at a median onset of 5 days. Two percent of patients also experienced grade ≥3 CRS. Additionally, 30% of patients had neurologic events, 10% of which were grade ≥3 at a median onset of 9 days. Grade 5 TEAEs related to treatment with liso-cel occurred in 4 patients, including, diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, and cardiomyopathy. Three grade 5 TEAEs were not related to liso-cel treatment including fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy. In 8 patients, there was ongoing CRS and neurologic events at their time of death of another cause. Thirty-seven percent of patients had prolonged grade ≥3 cytopenia.

TRANSCEND-NHL 001 is an ongoing multicenter, open-label, nonrandomized study. The coprimary end points are treatment-related adverse events, dose-limiting toxicities of liso-cel, and the ORR. The secondary end points are CR, DOR, PFS, OS, and health-related quality of life.¹

Patients with relapsed or refractory B-cell NHL who are aged 18 years or older are eligible to enroll given they have PET-positive disease by Lugano classification, and ECOG performance score of 0 or 1, an archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or at least 1 tumor-involved site deemed accessible at the time of screening, and adequate bone marrow and vascular function. These individuals may have previous CD19-targeted therapy but must have CD19-positive lymphoma which has been confirmed by a biopsy since the time of their prior therapy. The study excluded individuals who had prior treatment with corticosteroids, low-dose chemotherapy, cytotoxic chemotherapeutic agents, lymphotoxic chemotherapeutic agent, immunosuppressive therapies, donor lymphocyte infusions, radiation, and allogeneic hematopoietic stem cell transplantation within a certain number of day or weeks before starting treatment on the study. Patients with certain comorbidities were also excluded.

“There remains a critical need for additional therapies in large B-cell lymphoma, particularly for relapsed or refractory patients,” said Stanley Frankel, MD, senior vice president, Cellular Therapy Development, Bristol-Myers Squibb. “Based on the TRANSCEND NHL 001 data, liso-cel has the potential to expand treatment options for those affected by this aggressive blood cancer who did not respond to initial therapies or whose disease has relapsed. This BLA acceptance and Priority Review designation is an important step as we work to improve treatment for these patients in need.”

References

1. U.S. Food and Drug Administration (FDA) accepts for Priority Review Bristol-Myers Squibb’s Biologics License Application (BLA) for Lisocabtagene Maraleucel (liso-cel) for adult patients with relapsed or refractory large B-cell lymphoma [news release]. Princeton, New Jersey: Bristol-Myers Squibb; February 12, 2020.https://bit.ly/37ruQbs. Accessed February 12, 2020.
2. Bristol-Myers Squibb announces Liso-Cel met primary and secondary endpoints in TRANSCEND NHL 001 study [news release]. Princeton, New Jersey: Bristol-Myers Squibb; December 7, 2019.https://bit.ly/38ptnUx. Accessed February 12, 2020.