This article is more than 5 years old. Information may no longer be current.
CTL019 therapy conferred 90% remission rate in relapsed, refractory ALL
Chimeric antigen receptor-modified T cells that target CD19 induced complete remissions in 90% of pediatric and adult patients with relapsed and refractory acute lymphoblastic leukemia, according to study results.
“Our results support that CTL019 can produce long-lasting remissions for certain heavily pre-treated ALL patients without further therapy,” researcher Noelle Frey, MD, MSCE, assistant professor of medicine and an oncologist at the University of Pennsylvania Abramson Cancer Center, said in a press release. “For our patients who have already relapsed after stem cell transplants, or don’t have any options for donors, this option has provided new hope.”
The analysis included 25 pediatric patients (median age, 11 years) and five adult patients (median age, 47 years) with relapsed or refractory ALL. Patients received CTL019 therapy — or autologous T cells that are transduced with an anti-CD19 chimeric antigen receptor (CAR) — in doses ranging from 0.76x106 cells/kg to 20.6x106 cells/kg.
Ninety percent of patients (n=27) achieved complete remission 1 month after the CTL019 infusion. The patients in remission included two pediatric patients whose disease was refractory to blinatumomab (AMG103, Amgen), as well as 15 patients whose disease recurred after stem cell transplantation.
Six-month EFS was 67% (95% CI, 51-88) and 6-month OS was 78% (95% CI, 65-95).
Researchers detected CTL019 cells in the blood, bone marrow and cerebrospinal fluid of responding patients, and researchers calculated a 68% (95% CI, 50-92) probability that CTL019 would persist at 6 months. A quantitative polymerase chain reaction assay indicated patients with sustained remissions had detectable CTL019 sequences for up to 2 years.
The probability that a patient would have relapse-free B-cell aplasia — a pharmacodynamic measure of CTL019 function — at 6 months was 73% (95% CI, 57-94).
Stephan Grupp
Cytokine-release syndrome — a known adverse event associated with CAR T-cell therapy — occurred in every patient. Severe cytokine-release syndrome, which occurred in 27% of patients, was significantly associated with a greater disease burden at baseline (
“The patients who participated in these trials had relapsed as many as four times, including 60% whose cancers came back even after stem cell transplants. Their cancers were so aggressive, they had no treatment options left,” researcher Stephan Grupp, MD, PhD, professor of pediatrics at the University of Pennsylvania Perelman School of Medicine and director of translational research in the Center for Childhood Cancer Research at Children’s Hospital of Philadelphia, said in a press release. “The durable responses we have observed with CTL019 therapy are unprecedented.”
Disclosure: The study was funded in part by Novartis. See the study for a full list of the researchers’ relevant financial disclosures.
Perspective
Back to Top
However, some words of caution are warranted. The treatment comes with significant side effects, including cytokine-release syndrome and neurologic toxicity, requiring ICU management in a significant fraction of patients. This side-effect profile and the technical issues involved in engineering the therapeutic T cells likely will preclude wider dissemination to many other centers in the very near future; however, these obstacles undoubtedly can be overcome. More challenging will be overcoming resistance due to disappearance of the therapeutic T cells and/or via antigen escape. Indeed, these issues have been problematic in prior reports of CAR T-cell therapy for ALL. In fact, lengthy remissions in ALL do not necessarily equate to cure, and late relapse after this therapy may still be a significant problem. It remains to be seen whether CAR T cells may be curative on their own.
Nonetheless, this article highlights the enormous potential of CAR T-cell therapy. It already has salvaged numerous patients with few, if any, other therapeutic options. At the very least, CAR T cells will have considerable impact as a bridge to allogeneic stem cell transplantation and/or as the backbone of a combined chemotherapy/immunotherapy approach. Hopefully, moving this promising therapy up earlier in the treatment course of high-risk patients may yield even greater benefits.