Ibrutinib to Treat CLL/SLL

New Orleans—After at least a year of treatment with ibrutinib, more than 80% of patients with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) had a partial or complete response, according to an open-label extension of a phase 2 trial. In addition, grade 3 adverse events and serious adverse events declined after the first year of treatment.

Results were presented during a poster session at the ASH meeting. The poster was titled The Bruton’s Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Monotherapy Demonstrates Long-Term Safety and Durability of Response in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Patients in an Open-Label Extension Study.

In November, the FDA approved ibrutinib under its accelerated approval process to treat patients with mantle cell lymphoma (MCL) who have received prior therapy. The oral drug was designated as a breakthrough therapy provided to medications that offer a substantial improvement over existing drugs for a series of life-threatening disease. Bortezomib and lenalidomide are the other drugs approved for MCL, a rare form of non-Hodgkin lymphoma that affects fewer than 200,000 people in the United States. Ibrutinib inhibits the Bruton’s tyrosine kinase and inhibits the proliferation, migration, and adhesion to CLL cells.

In this analysis, the authors examined data from 148 patients with CLL/SLL in a phase 1 study in which they received ibrutinib in an ascending dose or in a phase 1b/2 trial in which they took a continuous dose of ibrutinib. Patients also continued taking ibrutinib on a daily basis during a long-term extension study.

Of the patients, 31 were treatment-naïve and at least 65 years of age, while 117 had relapsed/refractory disease. The median age was 71 years in the treatment-naïve group and 65 years in the relapsed/refractory group, while 0% and 71% of patients, respectively, received at least 3 prior therapies.

At a median treatment duration of 21.5 months, 109 of the 148 patients continued to take ibrutinib for more than a year. In addition, 6 patients in the treatment-naïve group and 49 patients in the relapsed/refractory group discontinued treatment because of disease progression, adverse event, or another reason.

The overall response rate was 83.1%, including 80.6% of patients in the treatment-naïve group and 83.8% of patients in the relapsed/refractory group. The authors defined the overall response rate as complete response, complete response with incomplete bone marrow recovery, nodular partial response, or partial response.

The median duration of response was not reached for the patients in either group who achieved at least a partial response following a median follow-up of 28.1 months in the treatment-naïve group and 23.9 months in the relapsed/refractory group. The authors defined the duration of response as the number of months from first documented partial response with lymphocytosis or better to disease progression or death or the date of last adequate disease assessment.

Within the first year of treatment with ibrutinib, 43% of patients had a serious grade 3 or higher adverse event, which declined to 32% after the first year. Further, within a year of treatment, 24% of patients had grade 3 adverse events and 8% had serious adverse events, which declined to 7% and 0% after the first year, respectively. Within a year, 12 patients had adverse events leading to discontinuation of ibrutinib, while 6 patients stopped taking the drug because of an adverse event after the first year of treatment.

Serious grade 3 or higher adverse events were found in 29% of treatment-naïve patients and 62% of relapsed/refractory patients. The most common grade 3 or higher adverse events were pneumonia (16.9%), hypertension (13.5%), neutropenia (11.5%), thrombocytopenia (7.4%), and diarrhea (5.4%).

Pharmacyclics, Inc. conducted this study.