Credit: Penn Medicine
In a small study, 90% of children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL) achieved remission after receiving CTL019, a chimeric antigen receptor (CAR) T-cell therapy.
Seven of these 27 patients ultimately relapsed, and 5 went on to receive additional therapy, including stem cell transplant.
Still, 15 of these heavily pretreated patients remained in remission at a median of 7 months of follow-up and did not require further treatment.
“[Patients] had relapsed as many as 4 times, including 60% whose cancers came back even after stem cell transplants,” said Stephan Grupp, MD, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“Their cancers were so aggressive they had no treatment options left. The durable responses we have observed with CTL019 therapy are unprecedented.”
CTL019 cells are a patient’s own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.
In all, 30 patients received CTL019, including 25 children and young adults (ages 5 to 22) and 5 adults (ages 26 to 60). Three patients had primary refractory disease, 5 had relapsed once, and 22 patients had relapsed 2 or more times. Eighteen patients had received an allogeneic stem cell transplant.
Twenty-seven patients achieved a complete remission after an infusion of CTL019. Nineteen patients remain in remission, 15 of whom received CTL019 alone. Follow-up ranged from 1.4 months to 24 months.
Tests in patients who experienced complete remissions showed that their normal B cells had been eliminated along with their tumors. The researchers noted that persistent absence of normal B cells following CTL019 treatment indicates continued activity of the CAR T cells.
“Our results support that CTL019 can produce long-lasting remissions for certain heavily pretreated ALL patients without further therapy,” said Noelle Frey, MD, of the University of Pennsylvania in Philadelphia.
However, 5 patients did seek additional therapy, 3 of whom proceeded to allogeneic stem cell transplants while in remission.
Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including 3 whose cancers returned as CD19-negative leukemia that would not have been targeted by CTL019.
At 6 months, the overall survival rate was 78%, and the event-free survival rate was 67%.
All of the patients experienced cytokine release syndrome (CRS) within a few days of receiving CTL019, but they all fully recovered.
Twenty-two patients experienced mild to moderate CRS, which included varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain. Eight patients developed severe CRS, which required treatment for low blood pressure and breathing difficulties.
Nine patients were treated with tocilizumab, an immunosuppressant that inhibits the effects of the inflammatory cytokine IL-6, which have been found to spike during the most robust phase of the CAR T cells’ expansion in the body. Six patients also received short courses of steroids to combat CRS symptoms.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. In July, the US Food and Drug Administration granted CTL019 breakthrough therapy designation for the treatment of relapsed and refractory adult and pediatric ALL.
The first multicenter trial of CTL019 recently opened in the US, and additional multisite trials are expected to begin by the end of the year.