Over a decade after receiving a treatment that modifies the immune cells to attack cancer, two early recipients of CAR T-cell therapy show no signs of cancer, according to a paper published Wednesday in Nature.

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What is CAR T-cell therapy?

In CAR T-cell therapy, providers remove a type of immune cell called T cells from a patient's blood, genetically modify them with receptors that target and destroy cancer cells, and then infuse the T cells back into the patient's blood. According to the New York Times, these therapies are promising treatments for certain cancers, but they do pose serious side effects—including cytokine release syndrome, neurological effects, high fevers, comas, dangerously low blood pressure, and even death. That said, these more severe symptoms have dissipated in most patients, the Times reports.

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Notably, the treatment does not work for all patients or all cancers. For instance, the treatment has not yet worked in patients who have solid tumors, such as the ones found in individuals with breast or prostate cancer.

So far, FDA has approved CAR T-cell therapies to treat several types of leukemia and lymphoma, as well as multiple myeloma, and clinical trials are ongoing for a range of other cancers, Axios reports.

CAR T-cell therapy may provide a 'cure' for some cancer patients

In 2010, three patients with chronic lymphocytic leukemia (CLL)—a cancer that starts in the bone marrow and slowly progresses to the blood—received CAR T-cell therapy at the University of Pennsylvania as part of a clinical trial to evaluate the treatment's safety and effectiveness.

When the trial began, the idea for this treatment "was way out there," according to Carl June, the principal investigator for the trial. In fact, June's own expectations for the survival rate of the T cells they were providing to patients in the trail were relatively low. "We thought they would be gone in a month or two," he said.

However, in a paper published Wednesday in Nature, June and his colleagues reported that two of the three trial participants, Doug Olson and William Ludwig, went into a remission within a year of the initial treatment—and neither Olson nor Ludwig had any sign of cancer over the subsequent 10 years. (Notably, Ludwig passed away in 2021 from Covid-19.)

For the treatment used in the trial, researchers genetically modified a subset of T cells called CD8 cells—known as "the assassins of the immune system," according to the Times—that get help from another group of T cells called as CD4 cells.

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Initially, researchers noted that these modified CD8 T cells almost immediately killed between three and a half and seven pounds of cancer cells in Ludwig's and Olson's bodies. Unexpectedly, however, the researchers observed that the CD8 cells remained in the patients' blood after attacking the patients' cancer cells and turned into CD4 cells—cells that in subsequent laboratory tests were able to kill B cells.

As John DiPersio, chief of the division of oncology at Washington University in St. Louis, who was not involved in the study, put it, these CD4 cells had surprisingly turned into assassin cells themselves or, "at least guardians that can keep the tumor cells at bay and undetectable in the patient for years."

Separately, June said Olson has no detectable leukemia cells. He noted that while leukemia cells may linger in Olson's body in very small quantities, only to be knocked back by CD4 cells "like whack-a-mole," he believes that "[t]he leukemia is gone" and the CD4 cells are just "stay[ing] on the job."

June added, "We need many more patients to be followed but at least in these two patients there is no more leukemia."

Not a cure-all for CLL, experts say

While enthused by Olson's experience, David Porter—Olson's oncologist at the University of Pennsylvania—cautioned that the therapy is not a cure-all for everyone with CLL.

Olson's results are "beyond my wildest imagination," Porter said. "Oncologists don't use words like 'cure' lightly or easily or, frankly, very often. I guarantee that it's not being used lightly. The patients we treated had far advanced disease."

That said, he added that "the biggest disappointment is that it doesn't work all the time."

In fact, according to the Times, among patients like Olson who have CLL, the treatment has historically been less successful. Roughly a third to a fifth of CLL patients have gone into remission with CAR T therapy, but many have had their cancer relapse—even after it disappeared completely.

"The question is not only why some patients relapse or are resistant to therapy but why are some patients cured?" said DiPersio.

Total cost of CAR T-cell therapy can exceed $1 million

In a separate study by Prime Therapeutics, researchers analyzed real-world data and found that the total cost of CAR T-cell therapies averages more than $700,000 and, in some cases, can total more than $1 million.

For the study, researchers over two and a half years analyzed 74 patients who received treatment for B-cell lymphoma. First, they performed an assessment to evaluate treatment episode costs starting 30 days before the treatments were administered. Then, they evaluated post-treatment clinical outcomes starting 56 days after the treatments were administered.

Throughout the initial treatment period, the study found that the total cost of care ranged from $350,000 to more than $2 million. The cost for CAR T treatment medication alone averaged $527,000—making up approximately 74% of the total cost during the initial treatment. However, researchers found that 12% of patients with post-CAR T events incurred a total cost of over $1 million.

"CAR T-therapies represent an incredible advancement in treating B-cell cancers," said Joseph Leach, SVP and CMO for Prime Therapeutics. "Given the cost and toxicity of these treatments, we need better information to understand who derives durable benefit as well as how to best treat those who progress following therapy." (Snyder, Axios, 2/2; Kolata, New York Times, 2/2; Antrim, Pharmacy Times, 4/13/2021)