Credit: Mary Ann Thompson
Single-agent ibrutinib can elicit a high response rate in patients with high-risk chronic lymphocytic leukemia (CLL), results of a phase 2 trial suggest.
The Bruton’s tyrosine kinase inhibitor prompted a 92% objective response rate in patients who had previously untreated or relapsed/refractory CLL with either 17p deletion (del 17p) or tumor protein 53 (TP53) aberrations.
Researchers reported this and other results of the trial in The Lancet Oncology.
“Ibrutinib treatment results observed in CLL patients with del 17p or TP53 aberrations are very encouraging given that these patients have a high relapse rate after chemotherapy and are in need of tolerable, effective, and durable treatment options,” said study author Mohammed Farooqui, DO, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland.
He and his colleagues studied 51 patients in this trial, 35 with previously untreated CLL and 16 with relapsed or refractory CLL. Forty-seven of the patients (92%) had del 17p, and 4 patients carried the TP53 aberration but did not have del 17p.
The study’s primary endpoint was overall response rate after 24 weeks. Secondary endpoints included safety, overall survival, progression-free survival, best response, and nodal response.
The median follow-up for all patients was 24 months (15 months for the previously untreated cohort). At 24 weeks, 48 patients were evaluable for response, assessed according to the modified IWCLL 2008 criteria.
Response rates
At 24 weeks, 92% (n=44) of the 48 evaluable patients achieved an objective response. Fifty percent of all evaluable patients achieved a partial response (n=24)—55% of previously untreated patients (n=18) and 40% of relapsed/refractory patients (n=6).
As for best response, 10% of all patients achieved a complete response (n=5)—12% of previously untreated patients (n=4) and 7% of relapsed/refractory patients (n=1). And 67% of patients had a partial response (n=32)—70% of previously untreated patients (n=23) and 60% of relapsed/refractory patients (n=9).
After 8 weeks on therapy, ibrutinib was associated with a more than 50% mean reduction in tumor burden in the bone marrow (44%), lymph nodes (70%), and spleen (79%). After 24 weeks of therapy, the rates of tumor burden reduction (> 50%) increased to 83%, 93%, and 95%, respectively.
Survival and safety
The estimated progression-free survival at 24 months for all patients on an intention-to-treat basis was 82%. Forty-two of the 51 patients (82%) continued on ibrutinib treatment without disease progression.
The estimated overall survival at 24 months was 80% for all patients—84% for previously untreated patients and 74% for patients with relapsed or refractory disease.
At the final follow-up, 8 (16%) patients had died—5 (10%) from progressive disease, 2 (4%) from infection, and 1 (2%) patient with a sudden, unexplained death that may have been treatment-related.
The most common adverse events (occurring in more than 30% of all patients) potentially related to ibrutinib were arthralgia (59%), diarrhea (51%), rash (47%), nail ridging (43%), bruising (33%), and muscle spasms (31%).
The most frequent grade 3 or 4 hematologic adverse events were neutropenia (24%), anemia (14%), and thrombocytopenia (10%). The most common nonhematologic grade 3 adverse event was pneumonia, which occurred in 3 patients (6%).
Nine patients (18%) discontinued treatment. The reasons for discontinuation included disease progression in 5 patients (10%) and death for 3 patients (6%).
This research was sponsored by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute; Danish Cancer Society; Novo Nordisk Foundation; National Institutes of Health Medical Research Scholars Program; and Pharmacyclics Inc.
Ibrutinib is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
