The U.S. Food and Drug Administration (FDA) granted breakthrough-therapy designation for CTL019, a chimeric antigen receptor T-cell therapy, for adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) for whom ≥2 prior therapies have failed them. The designation was based on results from the multicenter, phase II JULIET study, for which results have not yet been published.
CTL019 also received breakthrough-therapy designation for the treatment of pediatric and young adult patients with relapsed/refractory B-cell acute lymphocytic leukemia (ALL). The FDA previously granted a priority-review designation for CTL019 in this patient population based on findings from the global phase II ELIANA study, a multicenter trial conducted in the United States, and a single-institution trial.
The ELIANA trial demonstrated a rate of complete remission (CR) or CR with incomplete blood count recovery (CRi) of 82 percent with CTL019, with all patients achieving a CR/CRi becoming minimal residual disease-negative (95% CI 69-91; p<0.0001). CTL019 treatment also led to a 6-month OS rate of 89 percent (95% CI 76-95) and a disease-free survival rate of 60 percent. The ELIANA study enrolled patients from 25 centers in the United States, Europe, Asia, and Australia. At the time of the assessment, 50 patients (median age = 12 years; range = 3-23 years) received lymphodepleting chemotherapy (including fludarabine 30 mg/m2 daily for 4 doses and cyclophosphamide 500 mg/m2 daily for 2 doses) prior to CTL019 infusion (2.0-5.0×106 kg for patients ≤50 kg and 1.0-2.5×108 kg for those >50 kg). A majority of patients (56%) had undergone prior hematopoietic cell transplantation, and the median number of prior lines of therapy was three (range = 1-8 therapies).
Eighteen patients discontinued treatment because of death (n=6), relapse (n=5), beginning new therapy while in CR (n=5), or patient or guardian decision (n=2). Two deaths were reported within 30 days of treatment (1 from ALL and 1 from cerebral hemorrhage). Seventy-one percent of patients experienced an AE within the first 8 weeks of treatment, of which 68 percent were deemed treatment related.
Forty-eight percent of patients experienced grade 3 or 4 cytokine release syndrome (CRS), but researchers noted that there were no deaths related to CRS. Fifteen percent of patients experienced grade 3 neurologic and psychiatric AEs (including confusion, delirium, encephalopathy, agitation, and seizure), but no cerebral edema was reported.
Sources: Novartis press release, March 29, 2017; Novartis press release, April 18, 2017.