Novartis and Gilead Sciences on Sunday presented updated, longer-term findings at the American Society of Hematology (ASH) annual meeting from two studies of CAR-T cell therapies in patients with large B-cell lymphoma, with data showing that initial responses were sustained over time.
In August, Novartis' CAR-T cell therapy Kymriah (tisagenlecleucel) gained FDA approval for certain paediatric and young adult patients with acute lymphoblastic leukaemia, making it the first clearance of a gene therapy in the US. Meanwhile, the company filed an application in October seeking FDA approval of Kymriah for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant.
At the time of the filing, which was based on findings from the Phase II JULIET study, Novartis noted that Kymriah demonstrated a three-month overall response rate (ORR) of 45 percent, with 37 percent of patients achieving a complete response (CR) and 8 percent achieving a partial response (PR). The drugmaker reported at ASH that the CAR-T therapy was associated with an ORR of 53 percent, with 40 percent achieving a CR. Novartis added that for the 46 patients with at least six months of follow-up from infusion, the ORR was 37 percent with a CR rate of 30 percent, and a PR rate of 7 percent.
Results also showed that at month three, the CR rate was 32 percent and the PR rate was 6 percent, which remained consistent to month six, at 30 percent and 7 percent, respectively. According to Novartis, cytokine release syndrome (CRS) in the JULIET study occurred in 58 percent of all treated patients, with 23 percent experiencing grade 3/4 CRS. Meanwhile, 21 percent of patients experienced any grade neurologic events, and 12 percent had grade 3/4 neurologic adverse events.
"While we don't completely understand why these remissions are so durable, it's exciting and will change how this disease is treated when conventional therapies fail," remarked Stephen Schuster, lead author of the JULIET study. "Patients that are in complete remission by 3 to 6 months are going to have durable remissions," Schuster added.
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Gilead's Yescarta (axicabtagene ciloleucel), which the company gained via its $11.9-billion purchase of Kite Pharma, gained FDA approval in October for adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic treatment, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Clearance was based on data from the ZUMA-1 study, with results showing that 72 percent of patients treated with a single infusion of Yescarta responded to therapy, including 51 percent who achieved a complete remission.
At ASH, Gilead presented an updated analysis from 108 patients in ZUMA-1 who had been followed for a minimum of one year, with results demonstrating that 82 percent of patients had responded to Yescarta, including 58 percent of patients who had achieved complete remission. The company added that at a median of 15.4 months post-infusion, 42 percent of patients remained in response, including 40 percent in complete remission. According to Gilead, in the updated analysis, 12 percent of patients experienced grade 3 or higher CRS and 31 percent experienced neurologic toxicities.
Commenting on the findings, Sattva Neelapu, lead author of the ZUMA-1 trial, said the data "confirms that these responses can be durable and the ongoing responses at 24 months suggest that late relapses are uncommon. Patients who are in remission at 6 months tend to stay in remission."
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