SAN DIEGO – Chimeric antigen receptor T-cell therapy with tisagenlecleucel (Kymriah) is associated with a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma, an updated analysis of the JULIET trial showed.
Neil Osterweil/MDedge News
Dr. Richard Thomas Maziarz
After a median follow-up of 19 months, two-thirds of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had early responses to chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel remained in remission with no evidence of minimal residual disease, reported Richard Thomas Maziarz, MD, from the Oregon Health & Science Knight Cancer Institute in Portland, at the annual meeting of the American Society of Hematology.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression. No treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” he said in a briefing prior to presentation of the data in a scientific poster.
The updated study results were published simultaneously online in the New England Journal of Medicine.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL that had relapsed or was refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant or who experienced disease progression after transplant.
Interim results of the study were previously reported at the European Hematology Association Congress in 2017.
At that meeting, Gilles Salles, MD, PhD, from the University of Lyon (France), presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up. In this population, the best overall response rate was 59%. The 3-month overall response rate was 45%, consisting of 37% complete responses and 8% partial responses. Relapse-free survival at 6 months was 79% and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
In the most recent analysis, completed after a median time from infusion to data cutoff of 14 months, the investigators reported on efficacy in 93 patients who received CAR T-cell infusions.
The best overall response rate, the primary endpoint, was 52%, comprising 40% complete responses and 12% partial responses. The response rates were consistent across all prognostic subgroups, including age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 65%, and was 79% among patients who had complete responses.
The median duration of response had not been reached at the time of data cutoff; the median overall survival had not been reached for patients with a complete remission. Overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to CRS or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic cell transplantation or for whom such therapy was not successful have very few treatment options. For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up,” the investigators wrote in the New England Journal of Medicine.
The JULIET Trial is supported by Novartis. Dr. Maziar reported personal fees from Incyte, Kite Therapeutics, and Athersys.
SOURCE: Maziarz RT et al. N Engl J Med. 2018 Dec 1. doi: 10.1056/NEJMoa1804980.
