ASH 2017 | High response rates seen with CTL019 in R/R DLBCL: Juliet trial primary analysis

The 59^th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on December 9–12, 2017. On Monday December 11^th, an oral abstract session was held on “Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Immune-Based Therapeutic Approaches”. This session was moderated by Robert A Baiocchi, Ohio State University and Lode J Swinnen, Johns Hopkins University.

Abstract #577 was presented during this session titled “Primary Analysis of Juliet: A Global, Pivotal, Phase 2 Trial of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma” by Stephen J. Schuster, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, and colleagues. In the summary below, data from the live session at ASH is used and therefore may supersede information in the pre-published Abstract.

Study Highlights

• 147 eligible patients (median age = 56 years (22–76)) were included in the study who were diagnosed with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), progressed after more than two lines of chemotherapy and were ineligible for autologous stem cell transplant (auto-SCT)
• Patients received a single dose infusion of CTL019 (tisagenlecleucel); median, 3.1 × 108 (range, 0.1-6.0 × 108) cells
• CAR-T cells were centrally manufactured and delivered to patients at 27 centers in 10 different countries across 4 continents. The logistics of this involved using cryopreserved apheresis, central production facilities and a global supply chain, demonstrating feasibility of treatment distribution
• The primary endpoint was best overall response rate (ORR) including complete response (CR) and partial response (PR) and was evaluated by an independent review committee (IRC)
• At ≥3 months’ follow-up
  • Best ORR = 53.1% (95% CI, 42% to 64%; P < 0.0001)
  • CR = 39.5% and PR = 13.6%
• At 3 months’ follow-up
  • CR = 32% and PR = 6%
• 6 months’ follow-up of 46 patients
  • CR = 30% and PR = 7%
• Median duration of response was not reached
  • 6-month probability of being relapse free was 73.5% (95% CI, 52.0% to 86.6%)
• Median overall survival was not reached
  • 6-month probability of overall survival was 64.5% (95% CI, 51.5% to 74.8%

Safety

• Most frequent grade 3 or 4 adverse events (AEs) included; cytokine release syndrome (58%), cytopenias lasting more than 28 days (27%) and infections (20%)
• 3 patient deaths were reported that were considered unrelated to treatment

The JULIET study demonstrated high durable responses in patients with R/R DLBCL treated with tisagenlecleucel. The authors concluded that this data should support global regulatory submissions for this treatment in 2018. CTL019 received breakthrough therapy designation for adults with R/R DLBCL on 18^th April 2017 by the U.S. Food and Drug Administration (FDA).