May 1, 2018 Kymriah DLBCL Approval in the U.S. FDA

May 1, 2018 Kymriah DLBCL Approval in the U.S. FDA

On May 1, 2018, the FDA approved Kymriah for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL). Kymriah is a CAR-T immunotherapy. Previously, Kymriah was the first FDA-approved cell therapy for the treatment of patients up to 25 years old with refractory or relapsed (second or later) B-cell precursor acute lymphoblastic leukemia (ALL).

Therapy Name: Kymriah

Manufacturer: Novartis

Indication: For the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL)

Kymriah Therapy Description

Kymriah is a CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy, a one-time treatment that uses the patient’s own T-cells to fight cancer. It utilizes the 4-1BB co-stimulatory domain in the CAR construct to enhance cellular expansion and persistence.

Kymriah Clinical Trial Data

The FDA approval was based on a pivotal Phase 2 study called “JULIET,” an open-label, multi-center, single-arm trial that enrolled 160 patients with relapsed or refractory DLBCL who had received at least two prior lines of chemotherapy, including rituximab and an anthracycline, or had relapsed after an autologous hematopoietic stem cell transplant (HSCT).

Of these, 106 patients received Kymriah infusion. Among the 68 evaluable patients, the median age was 56 years, and 71% were male. 78% had DLBCL, and 22% had DLBCL transformed from follicular lymphoma (17% high-grade). 44% had previously received an autologous HSCT. The patients had a median of 3 prior lines of therapy. 44% relapsed within 12 months of their last therapy, and 56% had refractory disease. 90% had received bridging chemotherapy, with 66% receiving fludarabine and 24% receiving bendamustine.

The median time from leukapheresis to Kymriah infusion was 113 days (range 47-196). The evaluable patients received a median dose of 3.5 × 108 (range 1.0-5.2 × 108) CAR-positive viable T-cells.

The results showed that adult patients with relapsed or refractory DLBCL treated with Kymriah achieved an overall response rate (ORR) of 50%, with 32% achieving a complete response (CR) and 18% achieving a partial response (PR). The median duration of response was not reached.

Kymriah Adverse Reactions

Common adverse reactions included cytokine release syndrome (CRS), infections, fever, diarrhea, nausea, fatigue, hypotension, edema, and headache.

The approval of Kymriah for relapsed or refractory large B-cell lymphoma (LBCL) adds another treatment option for these patients, and we look forward to this therapy becoming available to benefit patients in our country.