Positive longer-term follow-up results have been reported from phase 3 studies of ibrutinib (Imbruvica, Pharmacyclics/Janssen Biotech) in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL). The findings included an analysis of outcomes from the RESONATE and RESONATE-2 trials, which showed that ibrutinib was associated with favorable progression-free survival (PFS) and overall survival (OS) regardless of the line of therapy (previously treated or treatment-naïve).
Other data included longer-term follow-up results from the HELIOS trial, which showed that ibrutinib in combination with bendamustine and rituximab (BR) continued to demonstrate superiority over time compared with placebo plus BR in patients with relapsed/refractory CLL/SLL, along with improvements in the quality of response.
The new data were presented on June 6 at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
An analysis of results from the RESONATE and RESONATE-2 trials showed that ibrutinib was associated with favorable PFS and OS outcomes as well as a high overall response rate (ORR) in previously treated and treatment-naïve patients with CLL/SLL, regardless of the line of therapy. Median PFS and OS were not reached in treatment-naïve or previously treated patients; 89% to 92% of patients treated with ibrutinib at the first or second line of therapy remained progression-free at two years. In addition, the ORR was high in both previously treated and treatment-naïve patients (92% and 91%, respectively). Data from the RESONATE and RESONATE-2 studies served as the basis for the 2014 and 2016 FDA approvals of ibrutinib for patients with CLL/SLL.
The most common adverse events in the studies that supported the FDA approvals of ibrutinib for patients with CLL/SLL included neutropenia, thrombocytopenia, anemia, diarrhea, musculoskeletal pain, nausea, rash, bruising, fatigue, pyrexia, and hemorrhage. Among ibrutinib-treated patients, 4% to 10% discontinued treatment because of adverse events, which included pneumonia, hemorrhage, atrial fibrillation, rash, and neutropenia (1% each). Adverse events leading to dose reductions occurred in approximately 6% of patients.
After a median follow-up period of 25.4 months, data from the HELIOS trial showed that the combination of ibrutinib and BR continued to demonstrate a significant improvement in investigator-assessed PFS (the study’s primary endpoint) compared with placebo and BR (75% vs. 21%, respectively) in patients with relapsed/refractory CLL/SLL (median not reached vs. 14.2 months, respectively; hazard ratio [HR]: 0.199; P < 0.0001). The updated investigator-assessed ORR for ibrutinib plus BR was 87% compared with 66% for placebo plus BR (P < 0.0001), and the rate of complete responses (CRs) and of CRs with incomplete bone marrow recovery (CRi) improved in the ibrutinib-plus-BR arm compared with the placebo-plus-BR arm (34% vs. 7%, respectively). OS was not reached in either arm (HR: 0.670; P = 0.587).
Ibrutinib is a first-in-class, oral, once-daily therapy that inhibits the Bruton’s tyrosine kinase (BTK) protein. BTK is a signaling molecule in the B-cell receptor signaling complex that plays a key role in the survival and spread of malignant B cells. Ibrutinib blocks signals that tell malignant B cells to multiply and spread uncontrollably.
Ibrutinib is being studied alone and in combination with other treatments in several blood and solid-tumor cancers. More than 6,000 patients have been treated with ibrutinib in clinical trials, and 14 additional phase 3 studies have been initiated.
The prevalence of CLL is approximately 115,000 patients in the United States, with approximately 15,000 newly diagnosed patients every year. SLL is a slow-growing lymphoma biologically similar to CLL in which too many immature white blood cells cause lymph nodes to become larger than normal. CLL and SLL are predominately diseases of the elderly, with a median age of 71 at diagnosis.
Source: AbbVie; June 6, 2016.