Primary analysis confirms interim findings of CTL019 in DLBCL
ATLANTA—The first chimeric antigen receptor (CAR) T-cell therapy approved in the US to treat children and young adults with leukemia is also producing high response rates in lymphoma, according to investigators of the JULIET trial.
They reported that tisagenlecleucel (formerly CTL019) produced an overall response rate (ORR) of 53% and a complete response (CR) rate of 40% in patients with diffuse large B-cell lymphoma (DLBCL).
Additionally, researchers say the stability in the response rate at 3 and 6 months—38% and 37%, respectively—indicates the durability of the therapy.
At 3 months, 32% of patients who achieved CR remained in CR. At 6 months, 30% remained in CR.
Researchers believe these results confirm the durable clinical benefit reported previously.
Stephen J. Schuster, MD, of the University of Pennsylvania in Philadelphia, presented the JULIET data at the 2017 ASH Annual Meeting (abstract 577).
“Only about half of relapsed diffuse large B-cell lymphoma patients are eligible for transplant,” Dr Schuster said. “[O]f those patients, only about a half respond to salvage chemotherapy, and a significant number of patients relapse post-transplant. So there is really a large unmet need for these patients, and CAR T-cell therapy is a potential agent [for them].”
The JULIET trial was a global, single-arm, phase 2 trial evaluating tisagenlecleucel in DLBCL patients. Tisagenlecleucel (Kymriah™) consists of CAR T cells with a CD19 antigen-binding domain, a 4-1BB costimulatory domain, and a CD3-zeta signaling domain.
The trial was conducted at 27 sites in 10 countries across North America, Europe, Australia, and Asia. There were 2 centralized manufacturing sites, one in Europe and one in the US.
Patients had to be 18 years or older, have had 2 or more prior lines of therapy for DLBCL, and have progressive disease or be ineligible for autologous stem cell transplant (auto-SCT). They could not have had any prior anti-CD19 therapy, and they could not have any central nervous system involvement.
The primary endpoint was best ORR using Lugano criteria with assessment by an independent review committee. Secondary endpoints included duration of response, overall survival (OS), and safety.
Study design and enrollment
Patients were screened and underwent apheresis with cryopreservation of their leukapheresis products during screening, which “allowed for enrollment of all eligible patients,” Dr Schuster said.
Patients could receive bridging chemotherapy while they awaited the manufacture of the CAR T cells.
“What’s important to note is that, early on in the trial, there was a shortage of manufacturing capacity, and this led to a longer-than-anticipated interval between enrollment and treatment,” Dr Schuster said. “This interval decreased as manufacturing capacity improved throughout the trial.”
When their CAR T cells were ready, patients were restaged, lymphodepleted, and received the tisagenlecleucel infusion. The dose ranged from 0.6 x 108 to 6.0 x 108 CAR-positive T cells.
The infusion could be conducted on an inpatient or outpatient basis at the investigator’s discretion, Dr Schuster said.
As of the data cutoff in March 2017, investigators enrolled 147 patients and infused 99 with tisagenlecleucel.
Forty-three patients discontinued before infusion, 9 because of an inability to manufacture the T-cell product and 34 due to death (n=16), physician decision (n=12), patient decision (n=3), adverse event (n=2), and protocol deviation (n=1). Five patients were pending infusion.
There were 81 patients with at least 3 months of follow-up or earlier disease progression evaluable for response.
Patient characteristics
Patients were a median age of 56 (range, 22–76), and 23% were 65 or older. All had an ECOG performance status of 0 or 1, 80% had DLBCL, and 19% had transformed follicular lymphoma.
