Tisagenlecleucel Elicits Complete Response in Diffuse Large B-Cell Lymphoma Patients

Novartis recently announced positive findings from the JULIET clinical trial, which explored the efficacy of tisagenlecleucel (Kymriah) in 81 patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL).

The investigators found that treatment with tisagenlecleucel led to sustained complete response in these patients, according to a press release.

Treatment with the gene therapy produced an overall response rate (ORR) of 53% for at least 3 months of follow-up. Of these individuals, 40% achieved a complete response rate (CR) and 14% achieved a partial response rate (PR), according to Novartis.

At 3 months of follow-up, the CR was 32% and the PR rate was 6%. The investigators said these results persisted through 6 months, according to the release. At 6 months, the investigators found that the ORR was 37%, with CR at 30%.

"At the time of trial enrollment, these patients with DLBCL had been through multiple rounds of chemotherapy and many had unsuccessful stem cell transplants, leaving them with few options and a poor prognosis," said principal investigator Stephen J. Schuster, MD. "With tisagenlecleucel, we have been able to significantly increase their chance of achieving and maintaining a sustained response without stem cell transplant, demonstrating the therapy's benefit in the treatment of this lethal blood cancer."

Novartis also said that response rates were consistent among patients administered the therapy, including those who had received a previous autologous stem cell transplant and those with double-hit lymphoma, a subtype of DLBCL that has a poor prognosis.

Notably, no patients required a stem cell transplant after treatment with tisagenlecleucel, according to the release.

Additionally, the relapse-free probability at 6 months was 74%, the investigators reported. However, the median duration of response and median overall survival was not reached at analysis.

"While immediate response to treatment is a marker for efficacy, patients and physicians need treatment options that provide sustained responses over time with a consistent safety profile," said Samit Hirawat, MD, head, Novartis Oncology Global Drug Development. "We look forward to continuing to work with health authorities to bring Kymriah to patients with relapsed or refractory DLBCL."

Approximately 58% of patients experienced cytokine release syndrome, a complication of CAR-T therapies that occurs when engineered cells become activated, according to Novartis. Another 21% of patients experienced neurologic events and other adverse events included cytopenia and febrile neutropenia.

In April 2017, tisagenlecleucel became the first gene therapy to receive FDA approval. It is indicated for the treatment of pediatric and young adult patients with refractory B-cell precursor lymphoblastic leukemia.

Novartis submitted an application to the FDA in October 2017 for tisagenlecleucel to treat adults with r/r DLBCL who are unable to receive, or relapse after, a stem cell transplant, according to the release. These results were included in filings with the European Medicines Agency as well.