Kymriah Approved for Adults with Relapsed or Refractory Large B-Cell Lymphoma

August 2018, Vol 8, No 8 - FDA Approvals, News & Updates


On May 1, 2018, the FDA approved a new indication for the immunotherapy tisagenlecleucel (Kym­riah; Novartis), a CD19-directed, autologous T-cell gene therapy, for the treatment of adults with relapsed or refractory large B-cell lymphoma for use after ≥2 systemic therapies, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Tisagenlecleucel was first approved by the FDA in August 2017 for the treatment of young patients aged ≤25 years with relapsed or refractory precursor acute lymphoblastic leukemia. This was the first time the FDA approved a genetically modified CAR T-cell therapy in the United States (also known as gene therapy).

This new indication was approved based on the JULIET study, a single-arm, open-label, multicenter phase 2 clinical trial of adults with relapsed or refractory DLBCL or DLBCL that was developed from follicular lymphoma. All patients had ≥2 previous lines of systemic therapy or had a disease that relapsed after stem-cell transplant.

All patients received 1 infusion of tisagenlecleucel after chemotherapy. Among the 68 eligible patients, the overall response rate was 50%, including a 32% complete response. After a median 9.4-month follow-­up, the estimated duration of response was not reached among patients who had complete response versus 3.4 months in those with partial response.

The most common side effects (>20%) included cytokine release syndrome (CRS), infections, fever, diarrhea, nausea, fatigue, hypotension, edema, and headache. Tisa­genlecleucel is associated with serious risks for CRS and neurologic toxicities.