IBRUTINIB TREATMENT FOR CLL

t the 2017 American Society of Hematology (ASH) Annual Meeting & Exposition, the 3-year follow-up data from the RESONATE-2 study (PCYC-1115/1116) were presented. The investigators found that patients with previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) reported sustained improvements in the measures of well-being with ibrutinib (Imbruvica) vs chemotherapy with chlorambucil (Abstract 1746).

Patient-Reported Outcomes

These new data provide the longest quality-of-life follow-up for ibrutinib to date using patient-reported outcomes. Patients reported their quality-of-life outcomes for fatigue, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Patients 65 years and older (median age, 73) were randomized to receive 420 mg of ibrutinib once daily until progressive disease or chlorambucil for up to 12 months. Median treatment duration was 34.1 months with ibrutinib vs 7.1 months with chlorambucil.

At a median follow-up of 3 years, ibrutinib treatment resulted in significantly longer progression-free survival (median, not reached vs 15 months with chlorambucil), with an 87% reduction in the risk of disease progression or death vs chlorambucil (hazard ratio = 0.130; 95% confidence interval: 0.081–0.208). The progression-free survival rate for ibrutinib was 85% vs 28% with chlorambucil. Greater and sustained improvements in patient-reported outcomes were observed with ibrutinib, resulting in significantly greater improvements over time vs chlorambucil.

In patients treated with chlorambucil with progressive disease, patient-reported outcomes improved after crossing over to ibrutinib. Approximately 87% of patients receiving ibrutinib (vs 52% receiving chlorambucil) had decreased/normalized lymphadenopathy within 2 months, which was sustained through 36 months, and disease symptoms, including fatigue and night sweats, improved more frequently for patients treated with ibrutinib. A greater proportion of patients with baseline cytopenia showed sustained hematologic improvement with ibrutinib vs chlorambucil for hemoglobin (90% vs 45%) and platelets (83% vs 46%).

Further data showed the burden of hematologic support medical resource utilization was less with ibrutinib than with chlorambucil in the first year and subsequently continued to decrease.

The most common adverse events of any grade with ibrutinib were diarrhea (47%), fatigue (33%), and cough (30%). Eight grade 3 or higher adverse events had a prevalence of less than 3% in ibrutinib patients and generally decreased or were stable over time. During the first year of treatment, patients treated with ibrutinib vs chlorambucil experienced less grade 3 or higher neutropenia (8% and 18%), anemia (6% and 8%), and thrombocytopenia (2% and 5%); other common grade 3 or higher adverse events were pneumonia (5% and 2%), hypertension (4% and 0%), and infections as combined term (17% and 8%). Grade 3 or higher bleeding occurred in 7% of ibrutinib patients over the 3-year follow-up. Adverse events leading to treatment discontinuation occurred in 16% with ibrutinib over 3 years vs 23% for chlorambucil over 7 months of therapy, respectively.

“In the RESONATE-2 study, patients who were treated with ibrutinib reported greater and sustained improvements in overall health and well-being and experienced decreased disease-related symptoms,” said Danelle James, MD, MAS, Head of Clinical Science, Pharmacyclics LLC. “For patients with chronic lymphocytic leukemia, a disease that affects primarily older patients, quality of life is an important consideration that should be factored into treatment choices initially and throughout long-term use.”