The role of various prognostic factors in CLL/SLL is not yet fully understood, including the implications of new genetic markers associated with high risk. Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor that is approved for the treatment of CLL patients who have received at least 1 prior therapy, and for patients with 17p deletion CLL. In results presented before the 56th annual meeting of the American Society of Hematology, updated efficacy results from the phase 3 RESONATE (PCYC-1112) study comparing ibrutinib to ofatumumab were reported.
In the phase III study 391 randomized patients received 420 mg daily of ibrutinib or ofatumumab daily, until disease progression or unacceptable toxicity for up to 24 weeks. During an interim analysis at the median follow up of 9.4 months, patients in the ofatumumab arm were provided access to the ibrutinib arm.
Comparatively, progression free survival (PFS) was significantly longer for ibrutinib compared to ofatumumab. Overall survival (OS) was significantly better for ibrutinib compared to ofatumumab, with 18-month OS rates of 85% and 78% respectively. Higher number of prior therapies (≥3) and 11q deletion were associated with significantly lower 12-month PFS rate for ofatumumab, but not for ibrutinib. The overall response rate (ORR) for ibrutinib versus ofatumumab was 90% to 25%. Compared to ofatumumab, ibrutinib improved 12-month PFS and ORR regardless of baseline genetics, complex cytogenetics, or number of prior therapies. No significant difference in 12-month PFS was observed in ibrutinib treated patients with or without del(17p) or for those who developed lymphocytosis compared to those without lymphocytosis. Median treatment duration was longer for ibrutinib versus ofatumumab and was 16 to 5 months respectively.
In this one on one comparison ibrutinib significantly outperformed ofatumumab in PFS, OS, and ORR in patients with CLL/SLL with at least one prior therapy. These results are consistent with previously published findings, and provide further evidence for the clinical utility of ibrutinib in patients with CLL.