SAN DIEGO — Ibrutinib monotherapy resulted in a significant median progression-free survival benefit in patients with relapsed or refractory chronic lymphocytic leukemia with 17p deletion after approximately 5 years of follow-up, according to study results presented at the ASH Annual Meeting and Exposition.
The results also demonstrated that patients with relapsed or refractory CLL with 11q deletion reached a significant median PFS at 5 years.
“[This is] the longest follow-up data that we have with ibrutinib,” Susan O’Brien, MD, medical director of the Sue and Ralph Stern Center for Cancer Clinical Trials and Research at UC Irvine Health, told HemOnc Today. “This data is updated from the original phase 2 study. There is now a median progression-free survival in the relapsed and refractory [patient population]. Each time [the results had] been updated, we had yet to reach a median PFS.”
O’Brien and colleagues assessed overall response rates – including partial response with lymphocytosis – of long-term ibrutinib (Imbruvica; Janssen, Pharmacyclics) use in patients with treatment-naïve (n = 31) and relapsed or refractory (n = 101) CLL. Patients received either 420 or 840 mg of ibrutinib once-daily until disease progression or unacceptable toxicity.
Thirty-four percent of patients with relapsed or refractory CLL had 17p deletion, 35% had 11q deletion and 78% had unmutated IGVH. Median time on study was 62 months for the treatment-naïve patient population and 49 months for the relapsed or refractory population. Sixty-five percent of the treatment-naïve group and 30% of the relapsed or refractory group continued ibrutinib therapy after approximately 5 years of follow-up.
Patients with relapsed or refractory disease had a median of four prior therapies. In that patient population, the median PFS was 52 months with 60 month estimated PFS rates of 43%.
“This was really striking because in a patient population with a median number of four prior regimens, historically with chemotherapy [patients] had been lucky to get 6 months,” O’Brien said.
Although median PFS was not reached in the treatment-naïve patient population, estimated PFS at 60 months was 92%. Median PFS was 55 months in patients with relapsed or refractory CLL with 11q deletion and 26 months for patients with 17p deletion.
Median PFS decreased as patients in the relapsed or refractory group received more previous regimens. Patients who had received one-to-two prior regimens had a median PFS of 63 months. The median PFS for patients who had received four or more prior regimens was 39 months.
Onset of grade 3 or higher treatment-emergent adverse events was highest in the first year of therapy and decreased during subsequent years, O’Brien said. The most frequent grade 3 or higher adverse events after approximately 5 years of follow-up were hypertension (26%), pneumonia (22%), neutropenia (17%) and atrial fibrillation (9%).
Complete response rates were observed in 29% of the treatment-naïve population and 10% of the relapsed or refractory population.
“Even though the remissions are durable – particularly in the relapsed or refractory group – they are [primarily] partial remissions rather than complete remissions,” O’Brien said. “One area going forward that people want to focus on is trying to get complete remissions because what that would allow you to do – potentially – is discontinue therapy. The way we give ibrutinib now is we give it continuously and it sort of makes sense because if the patient has some amount of residual disease, you usually are leery of stopping the therapy because you figure at some point they’ll lose their response and progress. But where there’s a lot of focus now – both because patients don’t want to be on therapy for years and these treatments are expensive – [on finding] an ideal scenario [where] we could give these drugs for a finite period. I think going forward what we want to try and do is increase the CR rates, not only to get the patient into complete remission because that’s a crucial step to an actual curative strategy.” – by Ryan McDonald
Reference: O’Brien SM, et al. Abstract 233. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: O’Brien reports receiving research funding from Pharmacyclics and consultancy and Honoria from Pharmacyclics and Janssen.