Published results confirm the efficacy of tisagenlecleucel in patients with relapsed or refractory diffuse large B-cell lymphoma.
Recently published results confirm the efficacy of tisagenlecleucel in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). According to the results of the JULIET study, patients with r/r DLBCL who were ineligible for, or had disease progression, after stem-cell transplantation had an overall response rate (ORR) of 52% after a median follow-up of 14 months.
DLBCL, the most common type of non-Hodgkin lymphoma, has high levels of response to first-line immunochemotherapy combinations containing rituximab, according to the study published in The New England Journal of Medicine. However, for patients who relapse and cannot tolerate high-dose chemotherapy or stem-cell transplantation as second-line therapy, the prognosis drops drastically, with a median overall survival of just 4.4 months. Tisagenlecleucel, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed high response rates in previous studies of patients with r/r DLBCL. To confirm those results, researchers conducted the JULIET study to evaluate the safety and efficacy of tisagenlecleucel in adult patients with r/r DLBCL.
In the JULIET study, 93 patients with r/r DLBCL were evaluable for efficacy. At 14 months from infusion, the best ORR was 52% among patients who had 3 months or more of follow-up or discontinued therapy before 3 months (40% complete response [CR] and 12% partial response [PR]. ORR rates at months 3 and 6 were 38% and 33%, respectively, and CR rates at months 3 and 6 were 32% and 29%, respectively.
At the follow-up time, median duration of response had not yet been reached; however, investigators predict relapse-free survival at 12 months to be 79% for patients who had a CR and 65% for all patients who had a response. Median progression-free survival (PFS) also was not reached in patients who had a CR. Predicted PFS rates were 83% for patients who had either a CR or PR at 3 months. Median overall survival (OS) for every patient who received an infusion was 12 months. The estimated probability of survival at month 12 was notably higher in patients who had a CR compared with the total study population (90% vs 49%).
Grade 3/4 adverse events that occurred frequently included cytokine release syndrome (22%), unresolved cytopenia by day 28 (32%), infections (20%), neurologic events (12%), and febrile neutropenia (15%).
Investigators also evaluated CD19 expression and biomarkers to find out if certain subgroups would have higher, more durable response rates. Patients who had low or negative CD19 expression also had responses to tisagenlecleucel, suggesting that low or undetectable CD19 expression may still be treatable. A biomarker analysis of PD-1, CD3, TIM3, and LAG3 also did not show significant differences between response rates for patients with high and low expression. Two exceptions were a small number of patients with the highest PD-1/PD-L1 interaction scores and a subgroup with high LAG3-postive T cells, none of whom responded to tisagenlecleucel or had rapid disease progression after treatment. Further investigation of this observation will be needed.
Tisagenlecleucel (Kymriah) was FDA approved in May 2018 for the treatment of adult patients with R/R large B-cell lymphoma following at least 2 prior line of therapy. The published results were previewed last year.
Schuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-46. doi: 10.1056/NEJMoa1804980.