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.
Pages like this
not linked directly; found by shared links- Key paperZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early
Shares BELINDA, ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma, ICANS (neurotoxicity), Cytokine release syndrome (CRS).
- Key paperTRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma
Shares BELINDA, ICANS (neurotoxicity), Cytokine release syndrome (CRS), CD19.
- Key paperMaude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL
Shares Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, Novartis, Cytokine release syndrome (CRS).
- InstitutionChildren's Hospital of Philadelphia
Shares Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, Novartis, Cytokine release syndrome (CRS).
- TrialELIANA
Shares Tisagenlecleucel, Cytokine release syndrome (CRS), CD19, Manufacturing cost and time for living and radioactive medicines.
- Key paperELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL
Shares Tisagenlecleucel, ICANS (neurotoxicity), Abramson Cancer Center, University of Pennsylvania, Novartis.
- Key paperZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors
Shares ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma, ICANS (neurotoxicity), Objective response rate (ORR), Cytokine release syndrome (CRS).
- PersonCarl H. June
Shares Tisagenlecleucel, Abramson Cancer Center, University of Pennsylvania, CD19, Diffuse large B-cell lymphoma.