Study finds pill may represent promising treatment for stubborn blood cancers

March 10, 2014, American Society of Hematology

A pill that suppresses a key regulator of cancer growth may provide hope to relapsed leukemia and lymphoma patients running out of treatment options for their aggressive, treatment-resistant disease, according to three reports* published online today in Blood, the journal of the American Society of Hematology.

Patients with blood cancer are typically administered a combination of chemotherapy and immunotherapy, the latter using the body's own immune system to help fight disease, as a first line of treatment. While chemotherapy has traditionally been successful in destroying , it is accompanied by many harmful side effects and typically develop resistance, prompting researchers to investigate new targeted therapies that may be able to block the production of cancer cells while leaving normal cells unharmed.

One such targeted therapy, called idelalisib, is a highly selective compound that, unlike chemotherapy, can target a specific mechanism that fuels cancer growth. Taken as a pill, idelalisib first targets and then blocks the expression of the delta isoform of the PI3 kinase enzyme, which is critical for the activation and survival of cancerous B cells. Idelalisib's narrow targeting of the PI3 kinase delta make it an attractive potential therapy for patients with cancers that form in the B-cell pathway such as (CLL), indolent non-Hodgkin lymphoma (iNHL), and (MCL). While idelalisib is currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of treatment-resistant iNHL, another drug in its class called ibrutinib, which specifically targets a different cell regulator, has been approved as a second-line therapy for CLL and MCL.

"Idelalisib is a part of a revolutionary new class of treatments that can hone in on a specific target without causing the wide range of side effects seen with chemotherapy," said study author Jennifer R. Brown, MD, PhD, Director of the Chronic Lymphocytic Leukemia Center at Dana-Farber Cancer Institute in Boston.

In three manuscripts published today in Blood, investigators present data from a large Phase I study evaluating the safety and efficacy of idelalisib in more than 150 patients with CLL, iNHL, and MCL. Before joining the trial, patients had received several previous treatments – some as many as 14 – that either failed to destroy the disease or provided only a temporary reprieve. After an initial study involving all trial participants, patients were separated into CLL, iNHL, and MCL disease cohorts and received varied doses of idelalisib. The therapy appeared to be effective, as patients suffered few side effects and demonstrated promising response rates, with 72 percent of CLL patients, 47 percent of iNHL patients, and 40 percent of MCL patients achieving either a complete or partial response.

"Considering the high number of previous therapies that these patients had received, higher than we sometimes see in comparable studies, the efficacy of idelalisib that we observed was remarkable," said study author Ian Flinn, MD, PhD, Director of the Hematologic Malignancies Research Program at Sarah Cannon Research Institute in Nashville and a widely recognized expert in lymphoma. "It was this initial excitement that has inspired further studies of this therapy in patients with treatment-resistant blood cancers."

While patients in the CLL and iNHL cohorts experienced significant and prolonged reduction of disease activity, patients with MCL, a more aggressive and treatment-resistant type of lymphoma, experienced less favorable responses. Despite MCL patients' high overall response rate of 40 percent to idelalisib, the duration of their response to the drug was not as impressive; only a small fraction (22%) enjoyed prolonged benefits. Despite the modest duration of survival facilitated by idelalisib in the MCL group, the strong response rate suggests that investigators have identified a key regulator of ; however, more research is needed to further understand the potential of this therapy in MCL patients.

"While idelalisib is unlikely to receive designation as a single-agent therapy in mantle cell lymphoma due to the short duration of response, the path forward will likely include administering it in combination with other agents or developing second-generation PI3 kinase inhibitors," said study author Brad S. Kahl, MD, Director of the Lymphoma Service at the University of Wisconsin Carbone Cancer Center in Madison. "This study offers a strong foundation for future research on idelalisib in this disease."

Explore further: Idelalisib shows promise in treating indolent non-Hodgkin lymphomas

More information:

Related Stories

Idelalisib shows promise in treating indolent non-Hodgkin lymphomas

January 22, 2014
Slow-growing, or indolent, non-Hodgkin lymphomas are difficult to treat, with most patients relapsing repeatedly and the disease becoming increasingly resistant to therapy over time.

Twice-daily pill could turn leukemia into a highly treatable disease

January 23, 2014
(Medical Xpress)—Use of a twice-daily pill could turn a deadly blood cancer into a highly treatable disease, according to scientists at Weill Cornell Medical College who led a multinational research team. Their findings ...

New protein-targeting drug shows promise in early trial for patients with high-risk CLL

May 17, 2013
A new oral targeted drug, idelalisib (GS-1101), has the potential to stave off the need for additional treatments for relapsed or treatment-resistant chronic lymphocytic leukemia (CLL), according to a study led in part by ...

Drug shows surprising efficacy as treatment for chronic leukemia, mantle cell lymphoma

June 19, 2013
Two clinical studies published in the New England Journal of Medicine with an accompanying editorial suggest that the novel agent ibrutinib shows real potential as a safe, effective, targeted treatment for adults with chronic ...

Ibrutinib continues strong showing against mantle cell lymphoma

June 19, 2013
In a major international study led by researchers at The University of Texas MD Anderson Cancer Center, the targeted therapy ibrutinib continues to show remarkable promise for the treatment of relapsed or refractory mantle ...

Study identifies key protein that helps prevent lung cancer tumors from being destroyed

March 4, 2014
(Medical Xpress)—Researchers at the Translational Genomics Research Institute (TGen) have discovered a protein, Mcl-1, that helps enable one of the most common and deadly types of cancer to survive radiation and drug treatments.

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.


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.