JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma
In adults with aggressive lymphoma after at least two prior treatments, tisagenlecleucel produced responses in 52% and complete responses in 40%, most of which lasted.
JULIET was an international single-arm phase 2 trial of tisagenlecleucel in adults with relapsed or refractory DLBCL after two or more lines of therapy who were ineligible for or had relapsed after autologous transplant. Of 165 enrolled, 111 were infused; 93 were evaluable for efficacy at the primary analysis. The best overall response rate was 52% with complete response in 40%; among responders the estimated relapse-free survival at 12 months was 65% and median duration of response was not reached. Grade 3-4 cytokine release syndrome occurred in 22% and grade 3-4 neurological events in 12%, with no deaths attributed to the product. Bridging chemotherapy was allowed. It supported approval of tisagenlecleucel in DLBCL in 2018, the second CD19 CAR-T for this disease.
- 165 enrolled, 111 infused, 93 efficacy-evaluable adults with relapsed/refractory DLBCL; 27 sites in 10 countries.
- Best overall response 52%; complete response 40%.
- 12-month relapse-free survival among responders 65%; median duration of response not reached.
- Grade 3-4 CRS 22%; grade 3-4 neurological events 12%; no treatment-related deaths.
- A third of enrolled patients never received the product, mostly because of disease progression or manufacturing issues.
JULIET, with ZUMA-1, showed that CAR-T could rescue a substantial minority of adults with chemotherapy-refractory lymphoma and that complete responders often stay in remission. The lower toxicity of a 4-1BB construct and the option of bridging therapy made it usable in a broader population. The high drop-out between enrolment and infusion remains a lesson about turnaround time.
- Single-arm; efficacy reported on infused patients, flattering the intention-to-treat picture.
- Lower response rates than in ZUMA-1, possibly reflecting product, patient selection or manufacturing time.
- Long vein-to-vein time (median about 54 days) meant many patients progressed before infusion.
- Later randomised second-line trial (BELINDA) was negative for this product.