The investigational chimeric antigen receptor (CAR) therapy CTL019 demonstrated promising activity in 2 pilot trials, eliciting complete remissions in 27 of 30 pediatric and adult patients (90%) with relapsed/refractory acute lymphoblastic leukemia (ALL). The results were announced by Novartis and the University of Pennsylvania's Perelman School of Medicine.
“These interim results, which supported the recent FDA breakthrough therapy designation, reinforce the potential CTL019 has as a life-saving therapy for patients with relapsed/refractory ALL,” Usman Azam, MD, Global Head, Cell & Gene Therapies Unit, Novartis Pharmaceuticals, said in a statement.
Of the 27 patients who experienced a complete remission, 19 remained in remission — 15 received no further treatment with CTL019 and 4 withdrew from the study to receive other treatment. At 6-month follow up, the event-free survival rate was 67% (95% CI, 51-88) and the overall survival rate was 78% (95% CI, 65-95). CTL019-modified T cells were detected in blood for up to 11 months, while the probability of persistence of the drug at 6 months was 68% (95% CI, 50-92).
In total, 25 pediatric patients (aged 5-22) and 5 adult patients (aged 26-60) in various stages of disease were treated. Twenty-six patients had B-cell ALL in a 1st to 4th relapse, 3 had primary refractory B-cell ALL, and 1 had relapsed CD19-expressing ALL. Three patients were refractory to blinatumomab. Patients were infused with autologous T cells transduced with CTL019 lentiviral vector at doses of 0.7-20.6x106
CTL019 cells/kg and were followed for 2 years.
“This represents the largest experience to date of CD19-CAR T cells and demonstrates the ability of this approach to achieve sustained complete responses in a patient population with few other treatment options,” Stephan Grupp, MD, PhD, lead investigator on the trial and professor in the Perelman School of Medicine at the University of Pennsylvania, said in a statement. “We are especially hopeful for those patients who remain in remission for 1-2 years without further therapy.”
All 30 patients in the study experienced cytokine-release syndrome, an inflammatory response caused by elevated levels of cytokines associated with T-cell activation and proliferation. In 22 of 30 patients, cytokine-release syndrome was classified as mild to moderate. After median follow-up of 7 months, 7 patients had died — none were associated with treatment.
“These studies are another promising development in CTL019's history,” Azam said. “With each new CTL019 milestone, we are one step closer to potentially offering these seriously ill patients an additional treatment option.”
CTL019 first generated excitement at the 2013 ASH Annual Meeting, when it demonstrated a complete remission (CR) rate of 86% in pediatric patients and 100% in adult patients with relapsed/refractory CD19-positive ALL.
The drug then received a breakthrough therapy designation in July for the treatment of patients with relapsed/refractory ALL. It was the first CAR therapy to receive this designation from the FDA.
Juno Therapeutics (which brings together Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, and Seattle Children’s Research Institute) is developing 3 separate CAR therapies: JCAR014, JCAR015, and JCAR017. Kite Pharma and the NCI are also collaboratively developing KTE-C19, another notable CAR therapy.