May 2, 2018, FDA approved Novartis’ cell therapy Kymriah (CTL019) to treat Relapsed/Refractory Large B-cell Lymphoma, including Diffuse Large B-cell Lymphoma (DLBCL), DLBCL Secondary to Follicular Lymphoma (FL), and High Grade B cell lymphoma.
It is worth pointing out that this is already the second indication of Kymriah (CTL019). Kymriah is a CAR-T product jointly developed by Novartis and the University of Pennsylvania and is the world’s first FDA-approved clinical treatment. The main therapeutic target is CD19, which plays a pivotal role in the treatment of hematological malignancies. In August 2017, CAR-T treatment ushered in a historic moment, the US FDA approved the first CAR-T product Kymriah for the treatment of patients with B-cell precursor acute lymphoblastic leukemia (ALL) under 25 years of age.
For the re-expansion of indications for Kymriah treatment, Professor Schuster of the University of Pennsylvania and the Abramson Cancer Center said: “The therapeutic goal of Kymriah is to achieve a sustained state of remission in patients with relapsed/refractory DLBCL (R/R-DLBCL). Approval of Kymriah for treatment of R/R-DLBCL, and hematologists provides a new tool for the treatment of R/R-DLBCL, which promises to achieve sustained remission in patients with R/R-DLBCL without bone marrow transplantation, and long-term survival.”
The FDA has expanded Kymriah’s clinical indications into relapsed/refractory large B-cell lymphomas based on good results from the JULIET study. The JULIET study is a global, multi-center, phase II clinical trial that took off at the ASH meeting in 2017 when the JULIET study updated results showing that Kymriah had an overall ORR of 53% patients with R/R-DLBCL, and complete remission rate (CR) reached 40%.
Currently, the JULIET study data is updated again. In the Kymriah efficacy analysis, a total of 68 patients with relapsed/refractory diffuse large B-cell lymphoma (R/R-DLBCL) can obtain data, and they were treated with Kymriah monotherapy. The results showed that the overall effective rate (ORR) of patients with R/R-DLBCL was 50%, with a complete response rate (CR) of 32%, a partial response rate (PR) of 18%, and a median duration of remission (DOR) not reached. Thus, Kymriah has a significant effect in the treatment of R/R-DLBCL.
In terms of safety, a total of 106 patients with R/R-DLBCL were included in the analysis. The overall incidence of adverse events (AEs) was about 20%. The most common 3-4 AEs were thrombocytopenia (40%) and infection ( 25%), cytokine release syndrome (23%), neurotoxicity (18%), and nausea and fatigue. In general, Kymriah is safe and AEs are mostly controllable.