FDA Approves Tisa-Cel for Third Indication, R/R Follicular Lymphoma

Tisagenlecleucel (tisa-cel) was approved to treat adults with relapsed or refractory (R/R) follicular lymphoma. This is the third indication for the therapy since it became the first FDA-approved chimeric antigen receptor T-cell therapy in 2017.

The FDA expanded the indication for tisagenlecleucel (tisa-cel), sold as Kymriah, with an approval of it to treat adult patients with relapsed or refractory follicular lymphoma (FL) after 2 or more lines of systemic therapy.

Tisa-cel, a chimeric antigen receptor (CAR) T-cell therapy, is now approved in 3 indications. It was already approved to treat B-cell precursor acute lymphoblastic leukemia (ALL) in certain pediatric and young adult patients and to treat adult patients with relapsed or refractory large B-cell lymphoma. Tisa-cel was also the first CAR T-cell therapy approved by the FDA in 2017.

Tisa-cel was approved by the European Commission earlier in May for the treatment of adults with relapsed or refractory FL after 2 lines or more of systemic therapy.

FL is a slow-growing non-Hodgkin lymphoma that affects 15,000 people in the United States annually. It is often incurable and tends to recur, requiring several treatments over the person’s lifetime. According to Novartis, patients with FL may be exposed to a median of 4 lines of treatment with an upper range of 13 lines.

“Patients with follicular lymphoma who relapse or don’t respond to treatment have a poor prognosis and may face a series of treatment options without a meaningful, lasting response,” Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in chronic lymphocytic leukemia and lymphoma in the Division of Hematology Oncology and director of the Lymphoma Program and Translational Research at the University of Pennsylvania’s Abramson Cancer Center, said in a statement. “This new, effective option for patients with follicular lymphoma may offer long-term benefit.”

Schuster was also the institutional principal investigator on the phase 2 ELARA trial, a single-arm, open-label trial, on which FDA based the approval. The results of the trial were published online in December 2021 in Nature Medicine.

ELARA followed 90 patients for a median follow-up of 17 months to evaluate the efficacy of the therapy. The trial found that 96% of patients treated with tisa-cel achieved a response. Overall, 68% of patients achieved a complete response and 85% of these patients still had a response 12 months after their initial response.

The study also evaluated 97 patients for safety at 21 months of median follow-up. ELARA found that although more than half (53%) of patients experienced any grade cytokine release syndrome (CRS), there were no cases of grade 3 or higher CRS. While 43% of patients experienced any grade neurologic events, only 6% of patients experienced grade 3 or higher. The most common adverse effects were CRS, infections, fatigue, musculoskeletal pain, headache, and diarrhea.

In addition, tisa-cel was infused into 17 of the 97 patients (18%) in the outpatient setting.

Tisa-cel was developed at the University of Pennsylvania Abramson Cancer Center, which led one of the largest US trial sites for ELARA. Now Penn is conducting clinical trials exploring the use of the CAR T-cell therapy to treat other cancers, including multiple myeloma, glioblastoma, mesothelioma, and ovarian and pancreatic cancer.

“The approval of Kymriah offers patients with relapsed or refractory follicular lymphoma a new treatment option and new hope for improving patient outcomes,” said Meghan Gutierrez, CEO at the Lymphoma Research Foundation. “Having this single infusion treatment option helps to transform the way healthcare providers approach this type of blood cancer and we commend those who have contributed to the acceleration of scientific research for the benefit of patients.”