Novartis Kymriah Demonstrates Durable and Robust Responses in Relapsed/Refractory Follicular Lymphoma: Long-Term Follow-Up Data from Phase II ELARA Trial

December 12, 2021 /BioValleyBIOON/ --NovartisNovartis recently presented subgroup analysis data with a median follow-up of 17 months from the Phase 2 ELARA study at the 63rd American Society of Hematology Annual Meeting (ASH 2021). The results showed,In patients with high-risk relapsed or refractory follicular lymphoma (r/r FL), the CD19 CAR-T cell therapy Kymriah (tisagenlecleucel) has demonstrated very high efficacy.The one-year progression-free survival (PFS) rate was 67%; for patients achieving complete response (CR), the one-year PFS rate reached 86%. Consistent with the initial analysis,Kymriah demonstrated significant safety, with no high-grade cytokine release syndrome (CRS) reported within 8 weeks of infusion., and no new safety signals were observed.

Kymriah is a product of the United StatesFDAThe first approved CAR-T cell therapy,Currently available in 30 countries worldwide, with over 350 certified treatment centers.Kymriah is a CD19-directed genetically modified autologous T-cell immunocellular therapy.Unlike conventional small-molecule or biologic therapies, CAR-T cell therapy is a living T-cell therapeutic product. The principle of Kymriah involves genetically modifying the patient's T cells to express a chimeric antigen receptor (CAR) designed to target the CD19 antigen, which is expressed on various types of bloodTumorAntigen proteins on the cell surface, including B-cell lymphoma andLeukemiaCell.

Subgroup analysis results presented at the ASH meeting showed:With a median follow-up of 17 months, Kymriah induced a high rate of durable responses in most high-risk disease subgroups, which typically have a very poor prognosis.Among the nine high-risk subgroups analyzed, except for three subgroups (progression of disease within 2 years [POD24], high total metabolicTumorIn addition to volume [TMTV] and having received ≥5 prior lines of therapy, Kymriah demonstrated well-maintained rates of complete response rate (CRR), overall response rate (ORR), and duration of response (DOR) in the majority of patients.

High and durable responses were observed in the overall population of the ELARA study, with a total of 94 evaluable patients.The median follow-up time was approximately 17 months. The CRR was 69% (95% CI: 60-78), the ORR was 86% (95% CI: 78-92), the 12-month progression-free survival (PFS) was 67% (95% CI: 56-76), and the 9-month DOR was 76% (95% CI: 65-84). For patients with complete response (CR), the 12-month PFS was 86% (95% CI: 74-92), and the estimated DOR rate was 87% (95% CI: 75-93).In the safety analysis (n=97), the safety profile of Kymriah continues to reflect the significant results from the earlier ELARA analysis. Within 8 weeks post-infusion, 48% of patients experienced cytokine release syndrome (CRS), with no patients experiencing CRS of grade 3 or higher as defined by the Lee scale. Neurological events occurred in 37% of patients (3% ≥ grade 3), and there were no treatment-related deaths.

In the ELARA trial, a separate analysis of hospitalization and intensive care unit patterns for inpatients and outpatients showed,Kymriah may reduce healthcare resource utilization for outpatients with r/r FL.Among patients treated in the outpatient setting (n=17), 35% did not require hospitalization within the first 2 months post-infusion; compared with patients receiving inpatient treatment, those treated in the outpatient setting had a lower median average length of stay (4 days [n=17] vs 12 days [n=80]). Additionally,Compared with inpatients, the average hospitalization cost after infusion for outpatients was significantly reduced.。

Currently, in the United States and the European Union, Kymriah’s supplemental Biologics License Application (sBLA) and Type II variation have entered the review process: for the treatment of adult patients with r/r FL who have previously received at least two lines of therapy. In the U.S., the FDA has granted Priority Review to the sBLA. Previously,FDAKymriah has been approved for the treatment of r/r FL.Regenerative MedicineAdvanced Therapy (RMAT) designation; the European Commission (EC) has granted Kymriah Orphan Drug Designation (ODD) for the treatment of FL. If approved, Kymriah will provide an important treatment option for patients with r/r FL. Meanwhile, r/r FL will become the third B-cell malignancy indication for Kymriah.TumorIndications.

This new indication application is based on the positive data from the pivotal Phase 2 ELARA trial. This is a single-arm, multi-center, open-label Phase 2 trial that evaluated the efficacy and safety of Kymriah in adult patients with R/R FL. The primary analysis dataset of this trial was presented earlier this year at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.TumorASCO Annual Meeting VirtualMeetingPublished on.

The results showed that the study observed a strong response rate in r/r FL patients who had previously received multiple therapies (median: 4 [range: 2-13]): the complete response rate (CR) reached 66%, and the overall response rate (ORR) reached 86%. The safety profile was remarkable, with no patients experiencing Kymriah-related cytokine release syndrome (CRS) of grade 3 or higher within the first 8 weeks post-infusion.

NovartisExecutive Vice President andTumorJeff Legos, Global Head of Hematology Development at Novartis, stated: "The ability to administer Kymriah in an outpatient setting may reduce the treatment burden for patients and their care teams. The extensive data on FL presented at the ASH Annual Meeting demonstrates that Kymriah has the potential to deliver transformative outcomes and positively impact the entire healthcare system." (Bioon.com)

Source of Original Text:Novartis Kymriah® demonstrates strong responses in high-risk patients with relapsed or refractory follicular lymphoma in extended study follow-up