Atlanta, GA—Targeting Bruton’s tyrosine kinase (BTK) in patients with chronic lymphocytic leukemia (CLL) resulted in high response rates, without severe toxicity, according to the results of 2 studies that were presented at the 2012 ASH meeting.
Data from one trial showed a 70% response rate in 116 patients treated with ibrutinib and a 22-month survival of 96% in previously untreated patients and 76% in the subgroup with relapsed/refractory CLL.
A second study reported at the meeting demonstrated objective responses in 83% of patients with high-risk CLL who were treated with ibrutinib.
“Ibrutinib has the potential to change the treatment landscape in CLL,” said John C. Byrd, MD, Director of Hematology at The Ohio State University Comprehensive Cancer Center in Columbus during a press conference.
BTK has emerged as a key player in the abnormal B-cell antigen receptor signaling that drives CLL and certain other B-cell diseases. Ibrutinib is one of several BTK inhibitors in development and is the farthest along in clinical investigation.
Dr Byrd presented results from a trial of ibrutinib monotherapy involving 85 patients with previously treated CLL and 31 treatment-naïve patients. All patients received 420 mg daily orally, which was associated with a 68% objective response rate (10% complete response [CR]) in the previously untreated patients and 70% (2% CR) in the relapsed/refractory group. In addition, 13% of the treatment-naïve patients and 4% of patients in the relapsed/refractory group had stable disease.
At 22 months, 96% of the treated subgroup remained alive, as did 85% of the patients with relapsed/refractory disease.
The second trial involved 40 patients with poor-prognosis CLL. The cohort included patients with a history of poor response to therapy and those with unfavorable genetics, said Jan Burger, MD, PhD, a hematologic oncologist at The University of Texas M.D. Anderson Cancer Center in Houston.
All patients received ibrutinib daily plus weekly infusions of rituximab during the first month, followed by once-monthly infusions thereafter. The regimen resulted in 1 CR, 32 partial responses, 2 minor responses, and no response in 2 patients. Two other patients had not been treated long enough for a response assessment.
Dr Burger characterized the ibrutinib- rituximab combination as highly active, not that several patients had particularly dramatic responses.
In both trials, ibrutinib was associated with low rates of severe toxicity. Dr Byrd reported a 13% incidence of grade 3/4 myelosuppression and grade 3/4 infection in 10% of untreated and 40% of relapsed/refractory patients.
Dr Burger reported 13 cases of grade 3/4 toxicity, including neutropenia, fatigue, pneumonia, insomnia, and bone pain.
Diarrhea was the most common adverse effect associated with ibrutinib in both trials, and cases were grade 1/2 in severity.
“Most side effects were modest and went away after the first couple of cycles of therapy,” noted Dr Byrd.