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Two Studies Show Efficacy of Ibrutinib in Hematologic Malignancies

Ben Leach
Published: Monday, Jun 24, 2013

Dr. John C. Byrd

John C. Byrd, MD

Patients with two different hematologic malignancies—chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL)—showed high response rates to therapy with the novel targeted therapy ibrutinib, further solidifying the safety and efficacy of a drug that has proven very promising in early clinical trials.

The results of both clinical trials were published in the New England Journal of Medicine.

Ibrutinib is a selective tyrosine kinase inhibitor of the Bruton’s tyrosine kinase enzyme, which is associated with apoptosis, cell adhesion, cell migration, and other cellular processes that can help a tumor survive. The drug also has little effect on healthy T cells. In addition to CLL and MCL, ibrutinib is being investigated in multiple myeloma, follicular lymphoma, and diffuse large B-cell lymphoma.

In the first study, a phase Ib/II trial, 85 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) received ibrutinib orally once daily, with 51 patients receiving a 420 mg dose and 34 patients receiving an 840 mg dose. The majority of these patients had high-risk disease and had received a median of four prior therapies.1

The study found that the overall response rate (ORR) in both treatment groups was 71%, with an additional 20% of patients in the 420 mg dose arm and 15% of patients in the 840 mg dose arm experiencing a partial response with lymphocytosis. After a follow-up of 26 months, the estimated rate of progression-free survival (PFS) was 75%, and the rate of overall survival (OS) was 83% for all patients, irrespective of the dose.

Most of the side effects were grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection.

“Essentially all CLL patients respond well to ibrutinib, which lacks many of the side effects of chemotherapy and frequently produces long-lasting remissions even in patients with high-risk genetic lesions,” said John C. Byrd, MD, director of the division of hematology and a CLL specialist at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and one of the study co-leaders, in a statement.

In the second study, 111 patients with relapsed or refractory MCL received a daily dose of 560 mg of ibrutinib. Patients enrolled in this phase II trial were divided into two groups: those who had received ≥2 complete cycles of prior bortezomib therapy and patients who had received <2 complete cycles of the therapy, including those with no prior bortezomib therapy. ORR was the primary endpoint, with duration of response, PFS, OS, and safety serving as secondary endpoints.2

The investigators observed an ORR of 68%, a complete response rate of 21%, and a partial response rate of 47%, with prior bortezomib having no effect on the rate of response. After a median follow-up of 15.3 months, the estimated median duration of response was 17.5 months (95% CI, 15.8–not reached), the median PFS was 13.9 months (95% CI, 7.0–not reached), and the median OS was not yet reached. At 18 months, the estimated rate of OS was 58%.

“This is remarkable because the last agent approved by the FDA for MCL had a 30% response rate,” says Kristie Blum, MD, associate professor of medicine, head of the OSUCCC – James lymphoma program, and senior author of the study, in a statement. “This trial suggests that ibrutinib could significantly improve the landscape of therapy options for MCL.”

The researchers said that grade 3 or higher hematologic events were infrequent. These included neutropenia (16%), thrombocytopenia (11%), and anemia (10%).

Earlier this year, ibrutinib received three separate breakthrough therapy designations from the FDA, which helps to facilitate an expedited review process for promising drugs that demonstrate a substantial improvement over existing treatments. This designation was granted to ibrutinib for the treatment of CLL or SLL with deletion of the short arm of chromosome 17, relapsed or refractory MCL, and Waldenström’s macroglobulinemia.


  1. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia [published online ahead of print June 19, 2013]. N Engl J Med. doi:10.1056/NEJMoa1215637.
  2. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma [published online ahead of print June 19, 2013]. N Engl J Med. doi:10.1056/NEJMoa13056220.

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