FDA Expands Kymriah Approval for Large B-Cell Lymphoma

On Monday, the FDA approved tisagenlecleucel (Kymriah) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who have relapsed or are ineligible for an autologous stem cell transplant (ASCT).

On Monday, the Food and Drug Administration (FDA) approved tisagenlecleucel (Kymriah) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have relapsed or are ineligible for an autologous stem cell transplant (ASCT).

The drug — formerly known as CTL019 – is the second to be approved for patients with DLBCL, the most common form of non-Hodgkin lymphoma, in more than 3 decades. It was granted a Priority Review by the FDA in January.

Approval of the chimeric antigen receptor (CAR) T-cell therapy is based on positive results from the multi-national phase 2 JULIET study, in which the drug reached an overall response rate (ORR) of 50% (95% CI, 38%-62%) in adult patients with DLBCL.

The complete response (CR) rate was 32% and the partial response rate was 18%. The median duration of response had not been reached.

All-grade adverse events (AEs) occurring in at least 20% of the 106 patients infused in the study included cytokine release syndrome (CRS), infections, pyrexia, diarrhea, nausea, fatigue, hypotension, edema, and headache. Grade 3/4 infections occurred in 25% of patients and there were cases of grade 3/4 thrombocytopenia (40%) and neutropenia (25%) that lasted more than 28 days.

Severe or life-threatening CRS occurred in 23% of the 106 patients who were administered tisagenlecleucel. Grade 3/4 neurologic events were reported in 18% of treated patients. These neurologic toxicities were managed with supportive care. Eleven percent of patients experienced severe or life-threatening encephalopathy. Neurological AEs were not associated with patient deaths and zero cases of cerebral edema resulted in patient death.

"The goal of Kymriah is to provide physicians with a therapy that has demonstrated durable response rates in relapsed or refractory DLBCL patients, a patient population that has endured multiple rounds of chemotherapy with many having experienced unsuccessful stem cell transplants," Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in Penn's Perelman School of Medicine and director of the Lymphoma Program at the Abramson Cancer Center, said in a statement.

"With this approval, physicians now have a meaningful therapeutic option that can achieve and maintain a sustained response without stem cell transplant along with a consistent safety profile," Schuster added.

Kymriah is a one-time autologous T-cell immunotherapy treatment. Each dose of it is a customized treatment created using an individual patient’s own T-cells. The T-cells are collected and sent to a manufacturing center where they are altered to include a new gene that contains a CAR. The CAR will direct the T-cells to target and eliminate leukemia cells that have CD19, a specific antigen, on the surface.

Once modified, the cells are infused back into the patient to kill the cancer cells.

Tisagenlecleucel is approved through the FDA Risk Evaluation and Mitigation Strategy (REMS) program. According to Novartis, the developer and manufacturer of the cancer therapy, the REMS program will inform healthcare professionals about the risks that could potentially be associated with the treatment.

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