Patients with chronic lymphocytic leukemia (CLL) with deletion of the short arm of chromosome 17 (del 17p) follow an aggressive clinical course and demonstrate a median survival of less than 2 years. Ibrutinib is a first-in-class inhibitor of Bruton’s tyrosine kinase (BTK), currently approved as treatment for CLL patients relapsed after one prior therapy or patients with del 17p at any line of therapy. Ibrutinib’s initial approval was based upon phase II data published in June 2013. The expanded approval is based upon results from the RESONATE trial comparing ibrutinib to ofatumumab.
At the 56th annual meeting of the American Society of Hematology (ASH), investigators presented the results of the phase II RESONATE -17 (PCYC-1117-CA) study investigating ibrutinib in relapsed CLL patients with deletion of 17p.
The study was designed to evaluate the efficacy and safety of single-agent ibrutinib as treatment of patients with relapsed or refractory CLL with del 17p or small lymphocytic leukemia (SLL). 144 patients (137 CLL patients, 7 SLL patients) were enrolled and received ibrutinib 420 mg once daily until progression. The primary endpoint was overall response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and safety of ibrutinib.
At a median follow up of 13 months, the median PFS and DOR had not been reached. At 12 months, 79.3% of patients were alive and progression-free, and 88.3% of responders were progression-free, with only 20 patients (13.9%) reporting progressive disease. At the time of data cut, the median treatment duration was 11.1 months, and 101 of 144 patients (70%) continued treatment with ibrutinib.
Efficacy results were consistent with earlier results, and the PFS compares favorably to that of treatment-naïve del 17p CLL patients receiving FCR or alemtuzumab. These results support ibrutinib as an effective therapy for patients with del 17p CLL/SLL.