EHA 2018: Tisagenlecleucel Demonstrates More Than 1-Year Durability of Response in Adults With Relapsed or Refractory DLBCL
Fourteen-month results from the JULIET clinical trial showed ongoing durable responses are achievable with tisagenlecleucel (Kymriah) when administered to adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This updated analysis was presented by Borchmann et al at the 23rd Annual Congress of the European Hematology Association (EHA) (Abstract S799).
Analysis Findings
The overall response rate (ORR) was 52% (95% confidence interval [CI] = 41%–62%) among 93 evaluable patients who were followed for at least 3 months or discontinued earlier. A complete response (CR) was achieved in 40% of patients and 12% achieved a partial response (PR). Of the patients in CR at month 3, 83% remained in CR at month 12, and the median duration of response was not reached, indicating sustainability of response.
“Advanced aggressive lymphoma patients who once faced a poor prognosis now have the possibility of sustained remission after a single course of therapy—a previously unimaginable and revolutionary breakthrough,” said the lead author of the updated JULIET analysis Peter Borchmann, MD, of the Department of Internal Medicine, University Hospital of Cologne, Germany. “With 14 months of data from JULIET, we are seeing that tisagenlecleucel may continue to redefine outcomes for patients with relapsed or refractory DLBCL.”
In the JULIET study, the relapse-free probability at 12 months after a patient's first response (n = 48) was 65% (95% CI = 49%–78%). In fact, 54% (13/24) of patients who had achieved a PR converted to CR, including 2 patients between months 9 and 12. Median overall survival (OS) was not reached for patients in CR (95% CI =17.9–NE). The OS rate at 12 months was 49% and median OS was 11.7 months among all infused patients (n = 111) (95% CI = 6.6–NE). The median time from infusion to data cutoff was 14 months with a maximum time from infusion of 23 months. At the time of data cutoff, no patients in response following treatment with tisagenlecleucel proceeded to stem cell transplant.
Within 8 weeks of infusion with tisagenlecleucel, grade 3/4 cytokine release syndrome (CRS), as defined by the Penn Grading Scale—a rigorous scale for grading CRS—was reported in 22% of patients (14% grade 3; 8% grade 4). Fifteen percent of patients received tocilizumab for treatment of CRS, including only 3% of patients with grade 2 CRS and 50% of patients with grade 3 CRS. CRS is a known complication of chimeric antigen receptor (CAR) T-cell therapy that may occur when the engineered cells become activated in the patient's body. CRS was managed globally using prior site education on implementation of the CRS treatment algorithm. No deaths due to cerebral edema were reported.
In this analysis, 12% of patients had grade 3/4 neurologic adverse events, which were managed with supportive care. Grade 3/4 cytopenias lasting more than 28 days, grade 3/4 infections, and grade 3/4 febrile neutropenia occurred in 32%, 20%, and 15% of patients, respectively.
“When we continued follow-up with DLBCL patients in the global JULIET study, we were extremely pleased that response rates were maintained a year or more after infusion with tisagenlecleucel, which was consistent with the durable responses seen in the pilot studies conducted at Penn,” said Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in Penn's Perelman School of Medicine and Director of the Lymphoma Program at the Abramson Cancer Center. “We look forward to continuing to follow these patients who we hope will remain in remission from their disease.”
Analyses to better characterize and predict severe CRS and neurologic events, including relationships with baseline clinical and laboratory parameters, dose, and cellular kinetics were also presented.
Fifty patients discontinued before infusion and the majority did so due to rapid progression of their disease or deterioration in their clinical status reflecting the acute and progressive nature of relapsed/refractory DLBCL. Twelve out of 165 (7.3%) enrolled patients could not be infused due to inability to manufacture an adequate dose of CAR T cells.
In May 2018, the U.S. Food and Drug Administration (FDA) approved tisagenlecleucel for the treatment of adult patients with relapsed/refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma based on data from the JULIET study.
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