Drug Combines Major Change in Treatment of Chronic Lymphocytic Leukemia

A combination of two drugs allows patients with chronic lymphocytic leukemia to live disease-free and alive longer than usual care, according to a Phase 3 clinical trial with more than 500 participants at Stanford Medicine and several other facilities.

The researchers believe that the results of the trial will likely change the future treatment of most people with common blood cancer.

"I have seen a marked improvement in my symptoms within two weeks of starting treatment, with little or no side effects," said Dan Rosenbaum, an elderly trial participant. 57 years old. "It's so amazing that it's almost hard to talk."

"These findings will pave the way for the treatment of chronic lymphocytic leukemia in a new era," said Tait Shanafelt, MD, professor of medicine at Stanford. "We found that this combination of targeted treatments is both more effective and less toxic than the previous treatment standard for these patients.It seems likely that in the future, most patients will be able to to completely give up chemotherapy. "

Shanafelt, a professor at Jeanie and Stewart Ritchie Universities, is the lead author of the study, which will be published Aug. 1 in The New England Journal of Medicine. The main author is Martin Tallman, MD, head of the Leukemia Department at Memorial Sloan Kettering Cancer Center.

Currently, CLL patients who are fit enough to tolerate aggressive treatment are treated intravenously with a combination of three drugs, two of which, fludarabine and cyclophosphamide, kill healthy and diseased cells by interfering with the replication of the drug. DNA, and another, rituximab, which specifically targets B cells that are unleashed in the disease. However, fludarabine and cyclophosphamide can cause serious side effects, including serious blood complications and life-threatening infections, which are difficult for many patients to tolerate.

Rituximab plus ibrutinib

The new combination drug combines rituximab with another drug, ibrutinib, which also targets B cells.

In the trial, 529 participants with newly diagnosed chronic lymphocytic leukemia were randomly badigned at a ratio of 2: 1 to receive either six cycles of ibrutinib and rituximab, followed by a total of a treatment with ibrutinib until the course of the disease, six cycles of traditional chemotherapy including fludarabine drugs. , cyclophosphamide and rituximab.

The researchers followed each of the participants, recruited from nearly 180 study sites across the country, for almost three years and recorded the duration of their "progression-free survival" or the period during which their disease had not been diagnosed. exchange. progress and their overall survival.

Rosenbaum, a partner in a global strategy consulting firm and a great tennis player, was one of the randomly badigned participants to receive the experimental treatment. He noticed a difference in his symptoms almost immediately.

"I did not realize how tired I was," he said in the weeks before his treatment. "I could barely play a single game of tennis and I would be shattered for days, my lymph nodes were so swollen that it was impossible to button the button from the top of my shirt collar." But soon noticed that I had a little more spring in my walk.After 10 days, the size of my lymph nodes was significantly improved.And after six weeks, my tumors were no longer detectable at the time. ;medical exam. "

The researchers found that 89.4% of participants who received the experimental drug combination still had no leukemia progression about three years later, compared with 72.9% of those who received the drug. traditional chemotherapy combination.

Difference in overall survival rate

They also found a statistically significant difference in overall survival between the two groups; 98.8% of those randomly badigned to receive the new drug combination were alive after three years, compared with 91.5% of those who received traditional treatment.

Although the incidence of serious adverse events related to treatment was similar between the two groups, infectious complications occurred more frequently in the group receiving traditional treatment.

"I have two children and I thought about participating in a clinical trial," Rosenbaum said. "But when I learned that traditional treatment had a low but significant risk of death from secondary infections, the decision became clearer. I had few side effects due to the combination of ibrutinib and rituximab, which was very manageable. a life changing experience. "

"This is one of those situations that we do not often encounter in oncology," said Shanafelt. "The newer treatment is both more effective and better tolerated, it represents a paradigm shift in the way these patients should be treated, and we can now relegate chemotherapy to a plan of withdrawal rather than to treatment." first intention. "