Drug Duo May Be an Advance Against a Common Leukemia

A two-drug combo helps patients with a common form of leukemia survive longer than the current standard of care, a new clinical trial finds.

The phase 3 trial of more than 500 U.S. patients with chronic lymphocytic leukemia (CLL) found that a combination of rituximab and ibrutinib extended patient survival.

Specifically, 89.4% of the patients who received the experimental drug combination did not have any progression of their leukemia about three years after treatment, compared with 72.9% of those who received the traditional chemotherapy combination.

As to overall survival, regardless of whether the disease had progressed or not, the trial found that three years after treatment, 98.8% of patients who received the two-drug combination were alive, compared with 91.5% of those who received the traditional treatment.

The research was led by Dr. Tait Shanafelt, professor of medicine at Stanford University, and will be published Aug. 1 in the New England Journal of Medicine. The study received funding from Pharmacyclics LLC, which makes ibrutinib.

Shanafelt and his team believe the results could change how most people with CLL are treated.

"These results will fully usher the treatment of chronic lymphocytic leukemia into a new era," Shanafelt said in a Stanford news release.

"We've found that this combination of targeted treatments is both more effective and less toxic than the previous standard of care for these patients," he added. "It seems likely that, in the future, most patients will be able to forgo chemotherapy altogether."

Patient Dan Rosenbaum, 57, was one of the participants randomly assigned to receive the dual drug treatment. In the news release, he said he felt an easing of symptoms very soon after the therapy began.

"I hadn't realized how fatigued I had become," Rosenbaum said. "I could barely play a single set of tennis, and I would be wiped out for days afterward. My lymph nodes were so swollen it was impossible to button the top button of my shirt collar. But within the first week of starting treatment, I noticed I had a little more spring in my step. After 10 days, there was a marked improvement in the size of my lymph glands. And after six weeks, my tumors were no longer detectable by physical exam."

The current standard treatment for CLL patients is an intravenous combination of three drugs -- fludarabine, cyclophosphamide and rituximab (FCR). Fludarabine and cyclophosphamide kill both healthy and cancerous cells by interfering with DNA replication, while rituximab targets immune system B cells that "run amok" in CLL, according to the researchers.

However, fludarabine and cyclophosphamide can cause significant side effects such as severe blood complications and life-threatening infections, the researchers said.

The new drug combination pairs rituximab with ibrutinib, which also specifically targets B cells.

"This is one of those situations we don't often have in oncology," Shanafelt explained. "The new treatment is both more effective and better tolerated. This represents a paradigm shift in how these patients should be treated. We can now relegate [traditional] chemotherapy to a fallback plan rather than a first-line course of action."

One expert in CLL care agreed that the findings might mark an advance.

"The major strength of this study is that it is a prospectively randomized comparison with the 'chemo-immunotherapy' combination FCR, in a large sample size," said Dr. Kanti Rai. He's a hematologist with the CLL Research and Treatment Program at Northwell Health Cancer Institute in New Hyde Park, N.Y.

The new study finds that the two-drug combo is now "superior" to the three-drug approach, Rai said. However, FCR might still work best in a subgroup of CLL patients whose cancer has certain genetic characteristics, he added.

-----------------------------------------------------------------------
Editor's Note:

If you have any suggestion to the content, 

please email: Julia.Zhang@ubmsinoexpo.com