Kymriah, a CAR T-cell therapy, was approved to treat certain pediatric and young adult patients who have acute lymphoblastic leukemia (ALL).
The Food and Drug Administration approved Kymriah (tisagenlecleucel) — a CAR T-cell therapy – for the treatment of patients 25 years or younger who have B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
This is the first approval for a chimeric antigen receptor (CAR) T-cell therapy, or any gene therapy, in the United States, according to an FDA press release.
The approval follows the advice of the FDA’s Oncologic Drugs Advisory Committee (ODAC) which voted 10-0 in a committee meeting in July to recommend approval of Kymriah for pediatric ALL.
“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Scott Gottlieb, M.D., said in a statement. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”
The primary efficacy analysis was based on phase 2 results from CCTL019B2202 (B2202), a single-arm, international trial of 63 patients who received a single dose of Kymriah. The targeted dose of each Kymriah infusion was 2.0 to 5.0 x 106 kg for patients less than 50 kg and 1.0 to 2.5 x 108 for those greater than 50 kg.
Overall remission rate was 82.5 percent (95 percent CI, 70.9-91.0) in treated subjects. Forty patients (63 percent) had complete remission (CR) and 12 (19 percent) had complete remission with incomplete hematologic recovery (CRi).
All patients who had CR or CRi were associated with negative minimal residual disease status in the bone marrow.
Investigators concluded that Kymriah was associated with clinically meaningful remissions. Estimated relapse-free rate among responders at month six was 75.4 percent. Median duration of response was not reached at a median follow-up of 4.8 months.
Eleven patients who had CR+ CRi relapsed after Kymriah prior to data cut-off and before any new cancer therapy. Two other patients relapsed after receiving both Kymriah and new cancer therapy. Of the 52 patients who had CR+ CRi, 29 were still in remission at the last assessment before the data cutoff.
Median event-free survival (EFS) has not been reached at a median follow-up of 5.6 months. Of 63 patients evaluable for efficacy, 20 (31.7 percent) had an EFS event. At a median follow-up of 6.9 months, overall survival has not been reached.
Sixty-eight patients were included in the safety review.
The most common, 5 percent or more, serious adverse events (AEs) recorded in the study were cytokine release syndrome (CRS), febrile neutropenia, hypotension, acute kidney injury, fever and hypoxia. Thirty-two patients (47 percent) experienced grade 3/4 CRS, and median duration was eight days. There were no deaths associated with CRS.
Ten patients (15 percent) experienced grade 3 neurotoxicity, and 18 experienced grade 3/4 infections within eight days of infusion. Three patients died within 60 days of infusion due to infections.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, M.D., PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”
In a separate action, the FDA has also expanded the approved of Actemra (tocilizumab) for the treatment of CAR T-cell—induced severe or life-threatening CRS in patients two years of age or older. The approval is based on data demonstrating that in clinical trials of CAR T-cell therapy, patients who received tocilizumab had complete resolution of CRS within two weeks following one or two doses of the treatment.