Ibrutinib: It’s Not Just for Leukemia

VBCC - January 2013, Volume 4, No 1 - ASH Annual Meeting
Audrey Andrews

Atlanta, GA—The investigational agent ibrutinib, which is making news in the treatment of patients with leukemia, demonstrated “unprecedented” single-agent activity in patients with relapsed or refractory mantle-cell lymphoma (MCL), according to the lead author of an international phase 2 study that was reported at the 2012 American Society of Hematology meeting.

“Ibrutinib produced the highest response rate ever observed with a single drug in the history of relapsed mantle-cell lymphoma,” said Luhua (Michael) Wang, MD, Associate Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine of The University of Texas M.D. Anderson Cancer Center, Houston. “Patients with all characteristics benefited across the board.”

Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is a critical kinase for lymphoma cell survival and proliferation. The drug is the first in the new class of BTK inhibitors.

The PCYC-1104-CA study is an ongoing international, open-label, phase 2, single-agent trial of ibrutinib in patients with relapsed or refractory MCL. Currently, 115 patients have been enrolled, including patients who are totally naïve to bortezomib (89.2%) or who have received fewer than 2 cycles of bortezomib (10.8%), and those who have been exposed to bortezomib (ie, have received at least 2 cycles). Patients were allowed to have received up to 5 prior lines of therapy.

The overall response rate to single-agent ibrutinib 560 mg daily was 68%, including 65% among the bortezomib-naïve population and 72% for patients who were exposed to bortezomib; complete response rates in these cohorts were 21%, 23%, and 22%, respectively.

“These responses have been durable, and the median duration of response has not been reached,” Dr Wang noted. “The response improved with longer follow-up, demonstrating the phenomenon of ‘incremental response.’”

All patient subgroups derived benefit from the BTK inhibitor, with responses observed in 64% of patients with bulky disease, 65% of patients with refractory disease, 70% of those who were not disease refractory, 66% of those who had received at least 3 prior regimens, 76% of patients with prior lenalidomide exposure, and 74% of patients with a high-risk score.

With longer follow-up among 51 patients treated for a median of 14.7 months, responses have increased over time, he emphasized. The overall response rate from the first analysis at 3.7 months to the 14.7-month point increased from 69% to 75%, with complete responses increasing from 16% of patients to 39%. This pattern was seen in bortezomib-naïve and bortez­omib-exposed patients alike.

“This is higher than the complete response rates we see in other subtypes of lymphoma, including [historically] in MCL. It is an unprecedented single-agent response rate,” Dr Wang pointed out.

Median progression-free survival was 13.9 months for the whole population. For responders, it has not been reached, whereas it is <7 months for patients who did not respond to treatment.

Ibrutinib was well tolerated, and treatment-emergent adverse events were consistent with the safety data that were previously reported for this investigational agent. Grades 3 and 4 events occurred in <5% of patients. Approximately 10% of patients experienced grades 1 and 2 confusion, epistaxis, petechiae, and ecchymosis.

Ibrutinib appears active in other lymphomas as well, including diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma. Relapsed or refractory patients with these tumors demonstrated response rates ranging from 23% to 44%; response rates rose to 55% with optimal dosing, other investigators reported at the meeting.

In summarizing his findings in patients with MCL, Dr Wang ex­pressed much optimism about ibrutinib in hematologic cancer. “I look forward to the future with excitement, caution, and confidence,” he noted.

Related Items
Comparative Effectiveness Research Should Reap Benefits for Oncology Care
Audrey Andrews
VBCC - October 2013, Volume 4, No 8 published on October 18, 2013 in Breast Cancer Symposium
Current Patterns and Costs of Treating Patients with Metastatic Breast Cancer
Audrey Andrews
VBCC - October 2013, Volume 4, No 8 published on October 18, 2013 in Breast Cancer Symposium
For Oncologists, Some Food for Thought in the New Era of Healthcare Reform
Audrey Andrews
VBCC - October 2013, Volume 4, No 8 published on October 18, 2013 in Breast Cancer Symposium
The State of Cancer Globally in 2013
Audrey Andrews
VBCC - October 2013, Volume 4, No 8 published on October 18, 2013 in ESMO 2013 Conference
Nearly 1 in 5 Patients with Cancer Reports Financial Distress
Audrey Andrews
VBCC - July 2013, Volume 4, No 6 published on July 25, 2013 in Economics of Cancer Care
Immunotherapies Take Center Stage in Melanoma
Audrey Andrews
VBCC - June 2013, Volume 4, No 5 published on July 1, 2013 in ASCO Annual Meeting
Immunotherapies Take Center Stage in Melanoma
Audrey Andrews
VBCC - News published on June 7, 2013
Sorafenib Effective in Metastatic Differentiated Thyroid Cancer
Audrey Andrews
VBCC - News published on June 7, 2013
NCCN Updates Its Clinical Practice Guidelines
Audrey Andrews
VBCC - May 2013, Volume 4, No 4 published on May 31, 2013 in NCCN Annual Conference
The Changing Oncology Landscape: Evolution or Revolution?
Audrey Andrews
VBCC - May 2013, Volume 4, No 4 published on May 31, 2013 in NCCN Annual Conference
Last modified: May 28, 2014
  • Rheumatology Practice Management
  • American Health & Drug Benefits
  • Value-Based Cancer Care
  • Value-Based Care in Myeloma
  • Value-Based Care in Neurology