Kymriah demonstrates consistent efficacy and safety outcomes in US patients with real-world experience in adults with r/r DLBCL.- Novartis

Novartis announced results from two analyses of real-world experience with Kymriah (tisagenlecleucel), the only CAR-T cell therapy approved in two distinct indications . These analyses are from a readout of a 15-year post-marketing study that add to and complement the rigor of the Kymriah pivotal trials with evidence of the Kymriah real-world experience in expanded groups of patients. When Kymriah was used in the real-world setting, efficacy and safety were consistent when compared to the pivotal trials, including the 24-month analysis of JULIET in adults with r/r diffuse large B cell lymphoma (DLBCL) and ELIANA in children and young adults with r/r B-cell acute lymphoblastic leukemia (ALL). The real-world experience data were presented at the 61st American Society of Hematology (ASH) annual meeting.

Real-world experience with Kymriah in adults with r/r DLBCL: Efficacy : Efficacy outcomes for patients who received Kymriah in the real-world setting were similar to those demonstrated in JULIET. In this analysis of 80 patients with r/r DLBCL for whom three or more months of post-infusion outcomes were available, the overall response rate (ORR) was 58% including 40% who achieved a complete response (CR). Median follow-up was 4.5 months. In the 24-month analysis of the JULIET trial, ORR was 52% and CR was 38% (N=115) .

Safety : The anticipation and management of adverse events of CAR-T cell therapy have been crucial to successful administration of this innovative and relatively new type of therapy. In this analysis of real-world experience with Kymriah (safety set, N=83), the rate of grade 3 or higher cytokine release syndrome (CRS) and neurologic events were approximately 4% and 5%, respectively, as compared to 23% and 11% in the JULIET clinical trial (safety set, N=115), suggesting safety outcomes appear more favorable. The real-world analysis used the grading scales ASTCT for CRS and ICANs for neurologic events, whereas the JULIET trial used the Penn Grading Scale for CRS and MedDRA SMQ for neurologic events. Further, for patients who had CRS, tocilizumab and corticosteroids were administered in 20% and 4% of patients, respectively, in the real-world setting, and in 27% and 19% of patients, respectively, in the JULIET trial. Some patients in the real-world setting received tocilizumab earlier than in the clinical trial experience, indicating earlier use of supportive care may mitigate rates of high-grade CRS9. A total of 14 DLBCL patients died after treatment, all due to disease progression, however no deaths were attributed to toxicities from Kymriah.

Patient and product characteristics :More patients in the real-word analysis had a worse performance status, and on average, these patients were older and had received more lines of therapy than those treated in the JULIET trial. Cell viability is one of many product release specifications for Kymriah. The commercial specification for the viability specification of Kymriah in the United States is set at greater than or equal to 80%. For all other markets where Kymriah is approved, the cell viability specification is greater than or equal to 70%. In this US real-world analysis, 29 of the 102 patients with evaluable data received product that was below 80% cell viability. Efficacy and safety for patients receiving product with cell viability below the commercial specification was the same as those receiving commercial Kymriah. These data on the use of Kymriah in r/r DLBCL in the real-world setting were presented in an oral session at the ASH annual meeting (Abstract # 766; Monday, December 9, 3:30 PM EST).