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 ASH 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.