Specifically, the agency’s Notice of Compliance covers relapsed or refractory patients with unspecified DLBCL, primary mediastinal (thymic) large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL resulting from follicular lymphoma.
Yescarta — developed by Gilead Sciences-owned Kite Pharma — is a CAR T-cell therapy, a type of treatment that involves collecting the patient’s own immune T-cells and modifying them to produce a chimeric antigen receptor, or CAR. The receptor targets CD19, a protein found at the surface of tumor cells, which improves the T-cells’ detection and killing of cancer cells.
“CAR T therapy is at the forefront of personalized medicine and in the treatment of lymphoid cancers,” John Kuruvilla, MD, an investigator and hematologist in the Division of Medical Oncology and Hematology at Princess Margaret Hospital, said in a press release.
Kuruvilla also mentioned his first-hand experience of how Yescarta “transformed the prognosis and outlook for a patient who would otherwise have limited treatment options.” The treatment, he added, “offers a reliable process that is completely customized for each individual patient.”
Elizabeth Lye, Director of Research & Programs at Lymphoma Canada, said Health Canada’s approval “is an important milestone as it provides new hope” for Canadians with relapsed or refractory large B-cell lymphoma.
The U.S. Food and Drug Administration approved Yescarta in October 2017 for the same indications.
Both U.S. and Canadian approvals were based on results from the ZUMA-1 Phase 1/2 trial (NCT02348216). Of 101 patients receiving Yescarta, 72% responded to treatment, with 51% achieving a complete response — or disappearance of all cancer signs — over a median follow-up period of 15.4 months.
Severe cytokine release syndrome (CRS) — a systemic immune reaction causing high fever and flu-like symptoms which are often life-threatening — was observed in 12% of patients, while 31% experienced severe neurologic side effects.
The most common severe or life-threatening side effects included altered brain function infections, CRS, and an impairment of language. Four patients died from: cardiac arrest during CRS, overactive immune cells called histiocytes and lymphocytes, intracranial bleeding associated with low platelet count, and pulmonary embolism (a blood clot in an artery connecting the heart to the lungs).
Serious side effects occurred in 55% of participants. The most common, in 2% of patients or more, included altered brain function, lung infection, fever, and pneumonia. Cardiovascular complications such as atrial fibrillation — a type of abnormal heart rhythm — cardiac arrest, and decreased blood pressure were also observed. Seventeen participants (16%) needed to be admitted into intensive care.
For a more complete list of adverse reactions from ZUMA-1, click here.
Of note, the median manufacturing time for Yescarta in the trial was 17 days, which is important given the potential rapid disease progression in these patients, Gilead said.