Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study.
Level 4 - case-series / case-control
Single-arm, open-label phase 2 trial without a concurrent control group
PubMed 34516954 · doi:10.1016/S1470-2045(21)00375-2
What was done
Adults (≥18 years, ECOG performance status 0–1) with histologically confirmed relapsed or refractory large B-cell lymphomas who were ineligible for, did not consent to, or progressed after autologous haematopoietic stem-cell transplantation were enrolled across 27 sites in 10 countries. Patients received a single intravenous infusion of tisagenlecleucel (target dose 5 × 10⁸ viable transduced autologous anti-CD19 CAR T cells). The primary endpoint was overall response rate (ORR, complete or partial response assessed by independent review committee via Lugano classification) post-infusion in all infused patients.
What was found
Among 167 enrolled patients, 115 received tisagenlecleucel infusion. At a median follow-up of 40.3 months (IQR 37.8–43.8): - Overall response rate: 53.0% (95% CI 43.5–62.4; 61 of 115 patients), with 39% (45 of 115) achieving a complete response as their best overall response. - Most frequent grade 3–4 adverse events: anaemia (45 [39%]), decreased neutrophil count (39 [34%]), decreased white blood cell count (37 [32%]), decreased platelet count (32 [28%]), cytokine release syndrome (26 [23%]), neutropenia (23 [20%]), febrile neutropenia (19 [17%]), hypophosphataemia (15 [13%]), and thrombocytopenia (14 [12%]). - Common treatment-related serious adverse events: cytokine release syndrome (31 [27%]), febrile neutropenia (seven [6%]), pyrexia (six [5%]), pancytopenia (three [3%]), and pneumonia (three [3%]). - Treatment-related deaths: none reported.
Why it matters
Provides long-term follow-up confirming durable response rates and safety for anti-CD19 CAR T-cell therapy in heavily pretreated, transplant-ineligible or post-transplant aggressive B-cell lymphoma.
Limits
Single-arm design without a direct randomized comparator. Substantial attrition occurred between enrollment (n = 167) and infusion (n = 115, a 31% non-infusion rate), which may introduce survival or selection bias. Restricted to patients with ECOG performance status 0–1.
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