JAK inhibitors producing significant response in myelofibrosis patients

December 6, 2010, Mayo Clinic

Two janus kinase (JAK) inhibitors are substantially improving treatment of myelofibrosis in patients, say Mayo Clinic researchers who are presenting results of several clinical trials at the 52nd annual meeting of the American Society of Hematology (ASH) Dec. 4 in Orlando.

Their findings suggest that both drugs, CYT387 and TG101348, effectively reduce spleen size and alleviate constitutional symptoms, major symptoms of this disorder, but that each have unique benefits.

According to Ayalew Tefferi, M.D., a Mayo Clinic hematologist and principal investigator for both clinical trials, results were both "surprising and pleasant" for CYT387, the first drug of its class to alleviate anemia in a substantial proportion of patients. TG101348 was also the first in its class to result in a measurable decline in JAK2 mutation burden and to substantially reduce high white blood cell and platelet counts, he says.

"These drugs represent smarter, targeted treatments that appear to make a substantial difference in treatment of this disorder," says Animesh Pardanani, Ph.D. (mayoresearch.mayo.edu/staff/pardanani_a.cfm), the lead investigator on both studies. One of the two studies being presented at ASH is longer-term follow-up on the use of TG101348 in 59 patients with myelofibrosis who are being treated at Mayo Clinic, Stanford University Medical Center, MD Anderson Cancer Center, Dana-Farber Cancer Institute, University of Michigan and University of California, San Diego.

The study concludes that after 12 cycles of treatment, 95 percent of patients had some reduction in the size of their spleen. Within that group, 26 percent had a 100 percent reduction. The study also found that of the 48 patients who had a JAK2 mutation, 23 (48 percent) had a reduction in mutation burden. Patients who completed 12 cycles of therapy had the most reduction. Thirteen patients (72 percent) had a median 50 percent decrease. That response has lasted more than a year, says Dr. Pardanani.

The researchers also found that 56 percent of patients treated with 12 cycles of TG101348 achieved normal white blood cell counts.

"TG101348 represents the first proof of principle that a selective JAK2 inhibitor can shut down a signaling pathway and reduce the burden of neoplastic blood cells," Dr. Pardanani says. "It also offers significant clinical benefit in that it decreases spleen size, controls excess blood cell counts in more than half of patients, and improves symptoms such as fatigue and night sweats."

In the second study being presented at ASH, 32 of 36 enrolled patients had completed at least one cycle of CYT387 therapy in a phase I/II clinical trial. Within this group of patients, 41 percent achieved an improvement in anemia, as defined by the International Working Group criteria. And 97 percent had some degree of spleen-size reduction (at least a 50 percent reduction in 37 percent of those patients).

"CYT387 not only works to reduce spleen size and to help with other symptoms, but it is the first in its class to show a significant response rate in anemia in myelofibrosis patients," Dr. Tefferi says.

"These drugs represent a very important step in the right direction in treatment of myelofibrosis," Dr. Pardanani says. "The initial responses have been very promising, but more work needs to be done to define their individual role in the treatment of this disease."

"We are still learning how to use these agents, such as understanding the precise doses and schedule of administering them," he adds. "We are also trying to see how to combine them with other classes of drugs that we know can be effective in myelofibrosis."

The research team is currently conducting more studies to validate these results, and move the drugs further toward studies that are required for consideration of Food and Drug Administration approval.

Related Stories

Recommended for you

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

Catching up to brain cancer: Researchers develop accurate model of how aggressive cancer cells move and spread

February 15, 2018
A brief chat at a Faculty Senate meeting put two University of Delaware researchers onto an idea that could be of great value to cancer researchers.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.