CTL019 induces durable responses in diffuse large B-cell lymphoma

An investigational chimeric antigen receptor T-cell therapy induced durable complete responses among adults with relapsed or refractory diffuse large B-cell lymphoma, according to interim results of a phase 2 study released by the agent’s manufacturer.

The single-arm, open-label, phase 2 JULIET study evaluated the safety and efficacy of CTL019 (Novartis) in adults with relapsed or refractory diffuse large B-cell lymphoma who progressed after two or more lines of prior chemotherapy, or who were ineligible for autologous stem cell transplant.

Most patients (60%) had received at least three lines of chemotherapy, and 51% had undergone stem cell transplant.

Overall response rate served as the primary endpoint. Secondary endpoints included OS, duration of response and PFS.

Researchers reported a 3-month ORR of 45%, including a 37% complete response rate and an 8% partial response rate. Complete responses remained stable from 3 months through data cutoff.

More detailed results will be presented June 14 at the International Conference on Malignant Lymphoma in Lugano, Switzerland.

Full data from the JULIET study are expected to be available later this year, and they will serve as the basis for regulatory submissions in the United States and Europe.

“The ORR seen in this early analysis is impressive for these heavily pretreated patients with relapsed/refractory DLBCL, who have limited treatment options,” researcher Stephen Schuster, MD, professor of hematology/oncology at Perelman School of Medicine at University of Pennsylvania and Penn’s Abramson Cancer Center, said in a Novartis-issued release. “The goal for these patients is achieving durable response. The most promising aspect of these data is that, at the time of this interim analysis, all patients with complete response at 3 months have remained in complete response.”

Serious adverse events included cytokine release syndrome (26%), neurologic adverse events (13%), cytopenias that lasted more than 28 days (21%) and febrile neutropenia (14%).

Three patients died of disease progression within 30 days of infusion.

Over the course of the study, manufacturing success rate improved to 97% for the last 30 patients.

“We are pleased the interim results from JULIET highlight the potential for CTL019 to elicit durable responses in patients with relapsed/refractory DLBCL, an area of high unmet need,” Vas Narasimhan, global head of drug development and chief medical officer for Novartis, said in the release.

The FDA previously granted priority review and breakthrough therapy designation review to CTL019 for this indication.