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Single-dose tisagenlecleucel offers long-term responses for acute lymphoblastic leukemia
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A single treatment of the chimeric antigen receptor T-cell therapy tisagenlecleucel led to long-term durable remission among pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia, according to updated results of the phase 2 ELIANA clinical trial.
“Our data show not only can we achieve longer-term durable remissions, and longer-term survival for our patients, but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job,” Shannon L. Maude, MD, PhD, pediatric oncologist at Children’s Hospital of Philadelphia and assistant professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, said in a press release.
Tisagenlecleucel (Kymriah, Novartis) — the first FDA-approved chimeric antigen receptor (CAR) T-cell therapy — is composed of a CD19 antigen-binding domain, a 4-1BB costimulatory domain, and a CD3-zeta signaling domain.
The FDA based tisagenlecleucel’s approval on results of the open-label, single-arm phase 2 ELIANA trial, conducted at 25 centers in the United States, Canada, Europe, Australia and Japan.
At the time of approval, 68 patients received tisagenlecleucel infusions, and 63 were evaluable for efficacy. Fifty-two patients (83%) achieved complete remission or complete remission with incomplete blood count within 3 months of infusion. Median duration of remission had not been reached (95% CI, 7.5 months-not estimable).
To determine long-term effects, researchers conducted an expanded analysis of ELIANA that included 75 patients infused with tisagenlecleucel and evaluated for safety and efficacy.
An overall remission rate greater than 20% at 3 months in the full analysis set served as the primary endpoint.
All patients who responded to treatment were negative for minimal residual disease assessed via flow cytometry. The overall remission rate was 81%.
Median duration of remission had not been reached.
“This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed,” Maude said in the release.
RFS among responders was 80% at 6 months and 59% at 12 months.
EFS was 73% (95% CI, 60-82) at 6 months and 50% (95% CI, 35-64) at 12 months. OS was 90% (95% CI, 81-95) at 6 months, and 76% (95% CI, 63-86) at 12 months.
Researchers observed persistence of tisagenlecleucel in the blood for a maximum of 20 months (median, 168 days).
Among all 75 patients, 73% experienced grade 3 and grade 4 adverse events related to treatment. Cytokine release syndrome occurred among 77% of patients; however, the effects were treatable, the researchers noted.
“Some of our patients got very sick, but we showed that most toxic effects can be short lived and reversible, with the potential for our patients to achieve durable, complete remissions,” Stephan A. Grupp, MD, PhD, lead investigator of the ELIANA trial and director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia, said in the release. “One of our more challenging questions — ‘Can we manage the serious side effects of CAR T-cell therapy?’ — was asked and answered in this global study.”
Forty-percent of patients experienced neurologic events and managed with supportive care. No reports of cerebral edema occurred. – by Melinda Stevens
Disclosures: The study was funded by Novartis. Maude reports personal fees from Novartis and nonfinancial support from ArticulateScience, LLC during the conduct of the study. Grupp reports grant support and personal fees from Novartis; nonfinancial support from ArticulateScience, LLC during the conduct of the study; and personal fees from Jazz Pharmaceuticals and Adaptimmune outside the submitted work. Grupp also reports a patent related to toxicity management for antitumor activity of CARs WO 2014011984 A1). Please see the full study for a list of all authors’ relevant financial disclosures.
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