John C. Byrd, MD
A 4-year follow-up of the RESONATE study, comparing the BTK inhibitor ibrutinib (Imbruvica) to ofatumumab (Arzerra), continues to demonstrate ibrutinib’s benefit in patients with chronic lymphocytic leukemia (CLL) who had at least 1 prior therapy.
At a median follow-up of 44 months for the ibrutinib arm, the progression-free survival (PFS) was significantly longer for ibrutinib compared with ofatumumab, at a median PFS not reached versus 8 months (HR, 0.133; P
<.0001; 3-year PFS 59% vs 3%), with significant benefit across subgroups. The PFS with ibrutinib for the 11q deletion subgroup reportedly had the most favorable outcome; however, it was not statistically different for patients with 17p deletion or 11q deletion or without these abnormalities.
At the time of analysis, 68% of patients randomized to ofatumumab crossed over to ibrutinib. The overall survival (OS) rate for ibrutinib at 3 years was 74%. The overall response rate (ORR) with ibrutinib was 91%, with complete remission (CR)/CR with incomplete platelet recovery rates (CRi)—now 9%—increasing over time.
John C. Byrd, MD, D. Warren Brown Chair of Leukemia Research, professor of Medicine, Medicinal Chemistry and Veterinary Biosciences, director, Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, was the lead author of the long-term findings. In an interview with OncLive
during the 2017 ASCO Annual Meeting, Byrd shed light on the game-changing efficacy of ibrutinib in CLL.
OncLive: Can you discusse the updated findings from the RESONATE study presented at this meeting?
The RESONATE study is the first randomized phase III study that reported out the first-in-class irreversible inhibitor ibrutinib. This was a randomized trial that compared ibrutinib in second or greater line to ofatumumab, a standard of care for patients with CLL at that time. Patients were randomized to 1 or the other therapy; at the initial part of the trial, there was not a crossover. After it was clear that ibrutinib had significant activity, loss of equipoise existed for the control, and a crossover was allowed. What was presented at the 2017 ASCO Annual Meeting was long-term follow-up—a median of 45 months for most patients and, for some patients, out as far as 4.5 years.
The results continue to show the response over time with ibrutinib. The ORR is currently 91%. There is a slight increase in complete remissions; most notably, the short-term results of progression-free survival (PFS) and overall survival (OS). The PFS at that median extended follow-up time still has not been reached for all the genetic groups. It appears that the 11q deletion group is doing the best. Although, when you look at all of the genetic groups of patients enrolled on the study, we still see all groups doing well and not statistically different.
With any new drug that’s given for a long time, we worry about toxicities emerging. What has been quite remarkable with long-term follow-up is that the toxicities being seen are very similar as to what was seen in the phase II study. There is an increased risk of atrial fibrillation with ibrutinib, increased bruising, bleeding, and rash, but those really have not increased over time with the initial report.