Kymriah Yields Long-Term, Durable Remissions in Pediatric ALL


Kymriah, which is the first FDA-approved CAR-T cell therapy, is showing promising results in pediatric patients with acute lymphoblastic leukemia.

CAR-T cell therapy was a big buzz phrase last year, with the first agent approved by the Food and Drug Administration (FDA) in August 2017.

And now, after more than a year, children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) treated with Kymriah (tisagenlecleucel) had durable remissions, which in turn means the drug can induce longer survival, according to updated results published in New England Journal of Medicine.

“Kymriah, the first FDA-approved CAR-T cell therapy, has shown the potential to be a definitive therapy, providing early, deep and durable remissions for children and young adults with relapsed or refractory ALL,” Samit Hirawat, M.D., Head of Novartis Oncology Global Drug Development, said in a press release. “These data are a testament to our commitment at Novartis for continued CAR-T cell therapy research to bring this therapy to as many patients as possible.”

The single-center phase 1 to phase 2a study of Kymriah demonstrated high rates of complete remission. However, the agent, formerly CTL019, was associated with serious, but reversible, toxicities.

Researchers from the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania (UPenn) conducted long-term follow-up of the ELIANA study — a phase 2, single-cohort, 25-center, global study designed to evaluate Kymriah in 75 pediatric and young adult patients with CD19-positive relapsed or refractory B-cell ALL.

They specifically looked at overall remission rates, or the rate of complete remission or complete remission with incomplete hematologic recovery, within three months or more of follow-up.

Patients treated with Kymriah demonstrated an overall remission rate of 81 percent within three months, of which all patients who had a response to treatment were found to be negative for minimal residual disease. Sixty percent of patients achieved a complete response, while 21 percent of patients had complete responses with incomplete blood count recovery.

Event-free survival was 73 percent at six months and 50 percent at 12 months, while overall survival was 90 percent and 76 percent over the same time intervals, respectively. Duration of remission was not reached at the time.

The researchers found Kymriah persisted in the blood of patients for as long as 20 months.

The most common adverse events included cytokine release syndrome (77 percent), pyrexia (40 percent), decreased appetite (39 percent), febrile neutropenia (36 percent) and headache (36 percent).

Grade 3 to 4 events suspected to be related to Kymriah treatment occurred in 73 percent of patients.

Thirty-five patients were admitted to the intensive care unit for the management of cytokine release syndrome - a known complication of Kymriah that may occur when engineered cells become activated in the patient’s body.

Neurological events occurred in 40 percent of patients within eight weeks of infusion, of which the 10 patients that had grade 3 were managed with best supportive care.

“We continue to be encouraged by the results demonstrated with Kymriah in a patient population who previously had limited treatment options, and now have the potential for durable remissions translating into longer-term survival,” lead study author Shannon L. Maude, M.D., Ph.D., Assistant Professor of Pediatrics at CHOP and Perelman School of Medicine at UPenn said in the release.

“Not only does this longer-term follow-up from the ELIANA study reinforce that this is a potentially paradigm-changing treatment, but it also contributes to the growing body of evidence which shows the critical role of cell function, expansion and ongoing persistence of Kymriah associated with the durability of clinical response.”

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