Cell therapy can now be used to treat a common type of blood cancer earlier after the Food and Drug Administration on Friday approved Gilead's Yescarta for adults with large B-cell lymphoma that's resistant to initial treatment or relapses within one year.
The approval is a first for what's known as CAR-T therapy — complex treatments constructed from individual patients' immune cells and genetically reengineered to better target cancers. Until now, CAR-T therapies, several of which are approved in the U.S. alongside Yescarta, were reserved for treating the sickest patients after they had run out of other options.
In the clinical study supporting the FDA's approval, Yescarta decisively outperformed chemotherapy and a stem cell transplant, a treatment regimen that's been the standard of care for relapsed or refractory large B-cell lymphoma for decades. Results showed Yescarta significantly extended "event-free" survival, which refers to the amount of time before disease progression, subsequent treatment or death, compared to standard care. After two years, 40% of Yescarta-treated patients were alive versus only 16% of those treated with chemo and a transplant.
The rates of treatment response and remission were also higher among study participants given Yescarta than those in the control group.
"The philosophy for treating large B-cell lymphoma in first- and second-line therapy is to go for a cure," said Jason Westin, a director of lymphoma clinical research at MD Anderson Cancer Center in Texas. "It appears, based on the data from [Gilead's study] that there's a much greater potential for that with CAR-T cell therapy than a quarter-century-old standard of care."
Westin was a principal investigator on the trial and has received research funding from Gilead.
Large B-cell lymphoma is the most common form of the blood cancer. Around 18,000 people are diagnosed each year in the U.S., between 30% and 40% of whom will have their cancer relapse or become resistant after initial treatment, usually chemotherapy and an antibody drug.
Until now, those patients would then typically receive high-dose chemotherapy and a stem cell transplant, which can result in long-lasting remission. But not all patients respond well enough to chemo to receive a transplant, and others may be ineligible.
With Friday's approval, Yescarta is now an available option, too, and its supporting clinical trial results could help establish it quickly. The National Comprehensive Cancer Network, a non-profit alliance of cancer centers in the U.S., this month recommended use of Yescarta for its newly approved indication, Gilead noted in a statement.
But there are some obstacles to use, as well. Yescarta is expensive, priced by Gilead at $373,000 per patient. While treatment is now widely covered by insurance, the cost can still present hurdles for patients, depending on their coverage plans.
Yescarta is also technically difficult to manufacture, requiring several weeks for Gilead to turn patient immune cells into a cellular drug ready for infusion. For patients whose cancers have returned aggressively, those weeks can be crucial and physicians sometimes turn to "bridging" chemotherapy while they wait for the CAR-T product.
Westin, the trial investigator, said that doctors generally know how to manage the process and noted that the challenge is similar to what they currently face in treating patients later on. For its part, Gilead said it has invested in manufacturing capacity ahead of the FDA's approval to better support supply.
Further, Yescarta can cause dangerous immune and neurological side effects that must be carefully managed.
"CAR-T cell usage really needs to be done at a center that has experience with cell therapy and management of toxicities," said Westin. "It's not something that I think is likely to be done in small office-based practices or community-based hospitals. This is likely to be done at larger centers."
Larger centers also typically handle stem cell transplants, the current treatment standard, Westin added.
According to Gilead, there are 112 centers in the U.S. that are currently authorized to administer Yescarta.
While Yescarta is the first CAR-T therapy approved for this use, it could soon have company. The FDA is set to decide whether to clear Bristol Myers Squibb's CAR-T treatment Breyanzi in early lymphoma this summer. Clinical testing of Breyanzi showed a similar benefit over chemo and stem cell transplant.
Editor's note: This story has been updated to include further specifics on the initial treatment regimen in large B-cell lymphoma.