July 20, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Santa Monica, Calif. – Kite Pharma recently noted the publication of data related to its anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for aggressive non-Hodgkin’s Lymphoma (NHL) including diffuse large B-cell lymphoma (CLBCL). The data was published in the journal Molecular Therapy.
This new publication follows up on data published in February 2015 in the Journal of Clinical Oncology.
The new research was published by James Kochenderfer, a researcher in the Experimental Transplantation and Immunology Branch of the NCI Center for Cancer Research and Steven Rosenberg, chief of the Surgery Branch at NCI’s Center for Cancer Research.
In the research, nine patients with chemorefractory aggressive NHL were given a single dose of anti-CD19 CAR T cells with a CD28 co-stimulatory domain. Of the nine, seven had responses that could be evaluated. In five of the seven patients, complete remissions (CR) were observed. Of the five CRs, four are ongoing from 38 to 56+ months after treatment. No chronic adverse toxicities have been tied to the CAR T cells except B-cell aplasia and hypogammaglobulinemia. In addition, three of four patients in ongoing complete remissions recovered normal polyclonal B cells, which indicates that durable CRs can be maintained without continued activity of the CAR T therapy.
“We are encouraged to see durable CRs ongoing for more than three years, which raises a possibility of cure, from a single infusion of anti-CD19 CAR T cells in patients with chemorefractory DLBCL, a population that previously had no curative treatment options,” said David Chang, executive vice president of Research and Development and chief medical officer of Kite, in a statement. “This study helps us to understand the long-term potential for this anti-CD19 CAR T cell therapy (axicabtagene ciloleucel) in the larger aggressive NHL patient population.”
This publication closely follows a U.S. Food and Drug Administration (FDA) advisory panel unanimously recommending approval of Novartis ’ CAR-T therapeutic, CTL019 (tisagenlecleucel) for B-cell acute lymphoblastic leukemia. Although the recommendation of the Oncologic Drugs Advisory Committee (ODAC) doesn’t guarantee the FDA will approve the therapeutic, it often does follow recommendations, especially unanimous ones. If approved, it would be the first gene therapy approved in the U.S. Approval is expected in September.
CAR-T is a labor-intensive process unique to each patient. T-cells, a type of immune cell, are collected from the patient’s blood. They are then frozen and shipped to a laboratory, where they are genetically engineered to attack the specific cancer, multiplied, refrozen and shipped back to the patient’s physician to be infused into the patient. Once infused, the T-cells quickly multiple and are already super-stimulated to attack the patient’s specific cancer cells.
CAR-T therapy is generally dramatically successful, as both the Kite studies and Novartis studies indicate. There are also risks. There have been patient deaths, notably those in Juno Therapeutics CAR-T program for JCAR015, which the company has since shuttered. Those patients died from cerebral edemas.
The most common severe reaction caused by CAR-T is called cytokine release syndrome, which causes fever and flu-like symptoms that at their worst can be life-threatening. There are also issues with cerebral toxicity that can cause seizures and delirium.
Companies working in the area have developed protocols for dealing with the side effects or for minimizing them. As part of its plan for commercializing the process, Novartis will limit the therapy to 30 to 35 medical centers in the U.S. and the oncology departments will receive extensive training. Novartis staffers will also follow each patient for up to 15 years.
As noted, the therapy is very effective. In a Novartis trial of 63 patients, 82.5 percent went into remission.
