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Ibrutinib Safe, Effective Against Untreated, Relapsed and Unresponsive Chronic Lymphocytic Leukemia

April 8, 2013
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  • Ibrutinib disrupts the CLL-driving B-cell receptor signaling pathway.
  • Phase II trial showed the drug was well tolerated and effective against CLL regardless of del 17p status.
  • The drug was effective against disease in blood, lymph nodes, spleen and bone marrow.

WASHINGTON, D.C. — The drug ibrutinib was well tolerated and highly effective in patients with untreated, relapsed and unresponsive chronic lymphocytic leukemia (CLL), according to phase II data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“The degree of tumor reduction achieved by once-daily oral therapy was impressive,” said Adrian Wiestner, M.D., Ph.D., investigator and head of the Lymphoid Malignancies Section in the Hematology Branch at the National Heart, Lung, and Blood Institute at the National Institutes of Health (NIH) in Bethesda, Md. “We have seen patients with more than 90 percent reduction of lymph node disease within just two months.”  

Many elderly patients with CLL are unable to tolerate current aggressive standard therapies, and those with a deletion in the short arm of chromosome 17, referred to as “del 17p,” have particularly poor outcomes with chemotherapy. These two CLL patient populations that are enrolled in the NIH phase II study have the greatest need for novel treatment therapies, according to Wiestner.

Ibrutinib is a selective inhibitor of Bruton’s tyrosine kinase, a component of the B-cell receptor signaling pathway that plays a key role in the development and progression of CLL. This study confirms the single-agent antileukemia activity seen in prior phase I/II studies and extends this experience, particularly in del 17p CLL, according to Wiestner.

He and his colleagues enrolled 53 patients with CLL into two cohorts — 29 patients with del 17p and 24 patients without del 17p who were aged 65 years or older. They assigned all patients to 420 mg of ibrutinib daily and evaluated response to the drug at six months and every six months thereafter, until disease progression.

Most adverse events were mild and included diarrhea, fatigue and rash in less than 13 percent of the patients.

At six months, 95 percent of patients showed at least a 50 percent reduction in lymph node disease, and all showed reduction in spleen enlargement, with a median reduction of 55 percent. In 26 patients for whom a bone marrow biopsy was done, tumor infiltration decreased by 82 percent. Absolute lymphocyte count decreased by a median of 62 percent. Using standard CLL response criteria, 52 percent of patients had a partial response. At 12 months, the estimated event-free survival rate was 94 percent.

Using blood and tissue samples of lymph nodes collected from 15 patients before and during ibrutinib treatment, Wiestner and his colleagues showed effective inhibition of B-cell receptor signaling and tumor proliferation, which was reduced by more than 80 percent, as measured by Ki67 staining.

“Ibrutinib was highly efficacious as a single agent in patients with untreated, relapsed and unresponsive CLL, irrespective of their del 17p status,” Wiestner said. “Responses appear to be durable, and the drug is effective against the disease in lymph nodes, spleen and bone marrow. This is important because existing therapies often fail to effectively eliminate cancer cells in these tissue sites. Targeted therapy for CLL is becoming a reality, and this new approach will greatly improve the lives of patients with this disease.”

This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute at the NIH.

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit

Media Contact:
Jeremy Moore
(215) 446-7109
In Washington, D.C.,
April 6-10, 2013:

(202) 249-4005

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