Correlative Analyses of Cytokine Release Syndrome and Neurological Events in Tisagenlecleucel-Treated Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients
Section snippets
Objective
We report a 24-month clinical update and correlative analyses between cytokine release syndrome (CRS)/neurological events (NE) and inflammatory markers for patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) treated with tisagenlecleucel in the JULIET trial (NCT02445248).
Design
JULIET is a single-arm, pivotal, phase 2 trial of tisagenlecleucel in adult patients with r/r DLBCL. The primary endpoint was overall response rate (ORR: complete [CR] + partial response). Peak (within 1 month of infusion) serum cytokine levels were correlated with rate/grade of CRS (Penn scale) and NE (Common Terminology Criteria for Adverse Events [CTCAE] v4.03) within 8 weeks of infusion.
Results
As of 11 December 2018, 115 patients were infused (99 evaluable for efficacy). ORR remained 54% (95% confidence interval [CI]: 43, 64), CR rate was 40% and median duration of response was not reached (NR; 95% CI: 10, –) at a maximum follow-up of almost 24 months from onset of response. Of 31 patients with CR at 6 months, 3 relapsed between 6-12 months and 1 relapsed beyond 12 months. Median overall survival for all 115 patients was 10.3 months (NR for patients in CR). Severe (grade 3/4) CRS and
Conclusions
With up to 24 months’ follow-up, tisagenlecleucel continued to demonstrate durable efficacy. Severe NE appeared to correlate with severe CRS. Trends in peak levels of several markers were noted with severe CRS and—to a lesser extent—severe NE.
Keywords
diffuse large B-cell lymphoma, DLBCL, CD19, cytokines, ABCL, aggressive B-cell lymphoma