Dr. Carl June, an oncologist with the University of Pennsylvania’s Perelman School of Medicine, garnered attention last month when he declared CAR T-cell therapy a “cure” for people with leukemia.
Doctors tend to avoid using the word “cure” when discussing cancers, including leukemia. “Cure” suggests the disease is entirely gone, when in fact leukemia may seem to disappear with treatment, then return — a situation known as a relapse. Instead of “cure,” most doctors prefer the term “remission,” which means all the signs and symptoms of cancer are undetectable.
Dr. June’s comments related to a study he’d worked on, published in Nature, about two people who’d undergone CAR T-cell therapy 12 years ago for CLL. According to the study, both Bill Ludwig and Doug Olson achieved complete remission in 2010 soon after undergoing the treatment — and never relapsed.
“We can now conclude that CAR T cells can actually cure patients with leukemia,” Dr. June said of the study results, according to OncLive. “The reason we can now say this is a cure, from a scientific point of view, is these are the most mature, the oldest results reported in the scientific literature.”
According to the nonprofit Leukaemia Care, most people with CLL will relapse at some point within the first five years of starting first-line chemo-immunotherapy treatment. Before joining a CAR T-cell therapy clinical trial in 2010, Ludwig and Olson had both received numerous other treatments.
Olson is now a distance runner and fundraises for the Leukemia & Lymphoma Society, and he recently celebrated his 75th birthday. Ludwig went on to travel the U.S. with his wife in a motor home and spend time with his family, including new grandchildren. He passed away in 2021 due to COVID-19 complications.
Like Dr. June, other experts have expressed optimism about CAR T-cell therapy’s potential for treating leukemia, based on this study and others. However, some are hesitant to frame the treatment as a cure. “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,” said Dr. David Porter, director of cell therapy and transplantation at Penn Medicine. He then added, "The biggest disappointment is that it doesn’t work all the time."
In a press release from the University of Pennsylvania, Dr. Jan Joseph Melenhorst — the study’s lead author — described CAR-T cell therapy as a “living drug.” Dr. Porter referred to it as a type of “personalized therapy.” That’s because CAR-T cell therapy uses a person’s own immune cells to target and kill leukemia cells.
T cells — also called T lymphocytes — are taken from a person’s blood. T cells are white blood cells that kill virus-infected cells and cancer cells. The harvested cells are then genetically modified to contain proteins known as chimeric antigen receptors, or CARs. CARs are designed to bond with certain proteins on tumor cells, equipping the T cells to better target and destroy the specific type of malignant B cells found in that person’s leukemia.
CAR T-cell therapy is not new, but it was considered an experimental therapy in 2010 when the two subjects of the study received it. Through the study, the authors gleaned some important new information about the therapy and how it works.
Significantly, researchers were struck by the fact that the CAR T cells were still actively on patrol in the participants’ systems after so many years, keeping cancerous B cells in check. “At this point 10 years on, we can’t find any leukemia cells, and the CAR T cells are still on patrol and on surveillance for residual leukemia,” Dr. Olson told OncLive.
Through the study, researchers also learned more about how the CAR T-cell population evolved in the study participants over time. The researchers found that, early on in CAR T-cell therapy, “killer” CD8-positive T cells were most prevalent, destroying malignant B cells. Over time, though, “helper” CD4-positive T cells — which trigger immune responses — became more dominant, contributing to long-term remission.
Dr. Olson acknowledged that the study looked at just two individuals who’d received the treatment, and that more studies are needed. “We need many more patients to be followed, but at least in these first two patients, 10 years on, there is no more leukemia,” he told OncLive.
Notably, CAR T-cell therapy has shown positive outcomes in other studies. “In some studies, up to 90 percent of children and adults with B-ALL [B-cell acute lymphoblastic leukemia] whose disease had either relapsed multiple times, or failed to respond to standard therapies, achieved remission after receiving CAR T-cell therapy,” according to the Leukemia & Lymphoma Society.
The therapy also has shown potential in treating other types of blood cancer, such as multiple myeloma, according to the Leukemia & Lymphoma Society.
“CAR T-cell therapy has been extremely effective for specific leukemias and lymphomas, and we look forward to continuing our efforts in these cancers, while also looking at their impact on solid tumors with research in this area to see more development in the coming years,” said Dr. Porter.
Types of CAR T-cell therapies currently approved by the U.S. Food and Drug Administration (FDA) include:
As noted by the Leukemia & Lymphoma Society, CAR T-cell therapy can cause side effects, including cytokine-release syndrome (CRS), which can cause nausea, fatigue, headache, chills, and fever. More serious symptoms include low blood pressure, rapid heartbeat, cardiac arrest, and kidney issues. Severe CRS requires treatment in intensive care.
CAR T-cell therapy can also be expensive. A study by Prime Therapeutics found that, among 74 individuals who received CAR T-cell treatment between Jan. 18 and June 2020, the average cost of care exceeded $700,000. For 12 percent of treatment recipients, the total cost of care was upwards of $1 million.
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