The U.S. Food and Drug Administration (FDA) has agreed to review Bristol-Myers Squibb’s request to approve the investigational CAR T-cell therapy lisocabtagene maraleucel (liso-cel) for treating adults with relapsed or refractory large B-cell lymphoma, who have received at least two prior therapies.
The company’s biologics license application (BLA) was granted a priority review status by the FDA, which will shorten the agency’s review time to six months, compared with the usual 10 months. The final decision is expected by Aug. 17.
“There remains a critical need for additional therapies in large B-cell lymphoma, particularly for relapsed or refractory patients,” Stanley Frankel, MD, senior vice president of cellular therapy development at Bristol-Myers Squibb, said in a press release.
“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,” he added.
The BLA application was submitted by Juno Therapeutics, a subsidiary of Bristol-Myers Squibb, and was supported by data from the Phase 1 trial TRANSCEND NHL 001 (NCT02631044), the largest study of its kind (for a CD19-targeted CAR-T cell therapy) to support an approval request to date.
The study evaluated the safety and anti-tumor activity of liso-cel (previously known as JCAR017) in 268 patients with aggressive forms of B-cell non-Hodgkin’s lymphoma — including patients with diffuse large B-cell lymphoma, high-grade lymphoma, primary mediastinal B-cell lymphoma and Grade 3B follicular lymphoma — whose disease had returned or had not responded well to other treatments.
At the time of the trial’s latest analysis, 256 of the patients had been assessed for efficacy. The results demonstrated that therapy with liso-cel cleared all detectable traces of cancer (complete response) in more than half of the patients (53%), and partially shrunk tumor volumes in another 20%.
Responses were similar across all patient groups and lasted a median of 13.3 months.
Overall, median survival was 21.1 months, and the median time to disease progression or death (a measure called progression-free survival, or PFS) was 6.8 months, which was “substantially longer than PFS from the immediate prior therapy,” the researchers wrote in an abstract with the findings.
Patients with no signs or symptoms of cancer (those who had a complete response to liso-cel) experienced even better survival, with 65.1% being progression-free and 85.5% being alive at one year.
Serious, life-threatening, or fatal adverse events occurred in 79% of the patients, and consisted primarily of low blood cell counts, including neutropenia (low levels of immune cells called neutrophils; 60%), anemia (37%), and thrombocytopenia (low platelet counts; 27%).
Cytokine release syndrome, or CRS, a widespread inflammatory response that can result from treatment with CAR T-cells, occurred in 113 (42%) of the patients, with six (2%) experiencing serious or life-threatening CRS.
Neurological side-effects were recorded in 30% of the patients, 10% of which were considered severe or life-threatening.
Four deaths occurred related to liso-cel and lympho-depleting chemotherapy, which is a brief course of chemo administered shortly before liso-cel infusions to prevent the immune system from attacking CAR T-cells and improve the treatment’s efficacy.
Liso-cel is a type of immunotherapy called a chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a novel type of treatment that involves collecting a patient’s own immune T-cells and genetically modifying them in the lab to target a specific cancer protein. This is done to enhance the ability of T-cells (immune cells with the ability to eliminate cancers) to identify and efficiently kill cancer cells. Typically, modified cells are expanded to millions and infused back into the patient, to help fight the tumor.
CAR T-cells in liso-cel specifically recognize CD19, a cell surface protein abundant on normal and malignant B-cells.
Previously, the FDA granted liso-cel the designations of breakthrough therapy and regenerative medicine advanced therapy for aggressive relapsing or refractory B-cell NHL. In Europe, the European Medicines Agency gave liso-cel access to its priority medicines program for relapsing or refractory diffuse large B-cell lymphoma.
