Novartis Kymriah Demonstrates 83% Overall Response Rate in Relapsed/Refractory Follicular Lymphoma in Phase II ELARA Trial

December 06, 2020 /Bio ValleyBIOON/ --Novartis(Novartis) recently announced the analysis data of two independent trials of CD19 CAR-T cell therapy Kymriah (tisagenlecleucel) for treating patients with advanced lymphoma at the 62nd Annual Meeting of the American Society of Hematology (ASH).

The first analysis stems from the interim analysis of the Phase II ELARA study, which was conducted in patients with relapsed or refractory follicular lymphoma (r/r FL) who had previously received multiple therapies (median: 4 [range: 2–13]). The data showed that after a minimum follow-up of 3 months, the complete response rate (CR) with Kymriah treatment was 65%, and the overall response rate (ORR) was 83%.

The second analysis stems from the JULIET Phase II study, with a median follow-up of 40 months, conducted in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). The data showed that the 2-year progression-free survival (PFS) rate for Kymriah treatment was 33%. Given the limited treatment options capable of providing durable remission in this patient population, this analysis represents an important finding.

Both analyses reaffirmed the safety profile of Kymriah, with no new short-term or long-term safety signals identified.

Kymriah isFDAThe first approved CAR-T cell therapy, and also the first CAR-T cell therapy approved for two different indications. This drug is a one-time treatment designed to enhance the patient's immune system to fight cancer. Currently, the approved indications for Kymriah include: (1) treatment of relapsed or refractory acute lymphoblastic leukemiaLeukemia(1) Pediatric and young adult patients (up to 25 years of age) with relapsed or refractory acute lymphoblastic leukemia (R/R ALL); (2) Adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

In April this year, based on the preliminary results of the ELARA trial,FDAGranted Kymriah for the treatment of R/R FLRegenerative MedicineRegenerative Medicine Advanced Therapy (RMAT) designation, reflecting the significant unmet medical needs in the patient population with relapsed or refractory follicular lymphoma (R/R FL).NovartisRegulatory applications for Kymriah in the treatment of relapsed/refractory follicular lymphoma (R/R FL) are scheduled to be submitted first in the United States and subsequently in the European Union in 2021. If approved, R/R FL will become the third B-cell malignancy indication for Kymriah.TumorIndications.

John Tsai, M.D., Global Head of Drug Development and Chief Medical Officer at Novartis, stated: “Novartis“Committed to continuing to explore the safety and efficacy of Kymriah in patients with advanced hematologic malignancies who have not achieved long-term remission despite prior treatment with multiple therapies. As our research into CAR-T cell therapy deepens, these new analyses demonstrate the potential of Kymriah to transform cancer survival rates for certain patients with advanced lymphoma.”

Image source: childrenshospital.org

——Interim Analysis of the ELARA Study:Efficacy was evaluable in 52 patients, with a median follow-up of 9.9 months. Kymriah demonstrated efficacy in the majority of treated patients. Specifically, after at least 3 months of follow-up, 65% (99.5% CI: 45.1–82.4) of patients achieved complete response (CR), meeting the primary endpoint. The overall response rate (ORR) was 83% (95% CI: 69.7–91.8). Among patients who achieved complete response, the vast majority (90%) maintained their response for ≥6 months.

Safety results showed that among the 97 patients evaluable for safety, no new safety signals related to Kymriah emerged. Cytokine release syndrome (CRS) occurred in 49% of patients (Grade 1: 29%; Grade 2: 20%), with no cases of Grade 3/4 CRS reported. For CRS management, 15% of patients received tocilizumab and 3% received corticosteroids. Neurologic events (NEs) occurred in 9% of patients, with 1% experiencing Grade 3/4 NEs. The median time to onset of CRS and severe NEs was 4 days and 8.5 days, respectively, and the median time to resolution was 4 days and 2 days, respectively. All NEs and CRS cases resolved with appropriate interventions. Three patients died due to progressive disease, with no treatment-related deaths reported. In the ELARA study, 18% of patients received Kymriah treatment in an outpatient setting.

—JULIET Study: Analysis with a Median Follow-up of 40 Months:Patients treated with Kymriah (n=115) demonstrated sustained and durable responses. Among the 61 patients who achieved a response to treatment, the relapse-free probability at 24 and 36 months was 60%, and the median duration of response (DOR) was not reached (95% CI: 10–NE). The 2-year progression-free survival rate was 33%. The survival probabilities at 24 and 36 months were 40% and 36%, respectively. Importantly, no new safety signals were identified during long-term follow-up exceeding three years.

In this analysis, the researchers also evaluated biomarkers (such as tumor andTumorRelationship between baseline Myc overexpression in the tumor microenvironment (TME) and response to Kymriah therapy. Analysis showed that patients with negative Myc expression had a better prognosis compared to those with Myc overexpression. Myc overexpression leads to an adverse immunosuppressive TME and restricted T-cell responses. These results are consistent with historical outcomes in patients with Myc-negative and Myc-positive expression. Further determination of CAR-T cell therapy responseBiomarkersAnalysis is ongoing.(Bio Valley Bioon.com)

Original Source: Novartis analyses confirm benefit of Kymriah® with clinically meaningful rates of complete response seen in patients with certain advanced lymphomas