Ibrutinib dose adherence associated with higher PFS for CLL

Taking ibrutinib at full dose and on schedule improved PFS among patients with chronic lymphocytic leukemia, according to an analysis of the RESONATE trial presented at the Oncology Nursing Society Annual Congress.

“Patients who missed 8 or more consecutive days of ibrutinib oral chemotherapy experienced a higher rate of progression events as opposed to those patients who did not have a drug hold for longer than 1 week," Sarah Deisinger, RN, BSN, told HemOnc Today. “What we can take away from this study, as providers, nurses and other medical professionals, is the critical importance of educating outpatients on oral drug adherence. This includes the ability to be transparent with our patients in regard to treatment outcomes for drug holds greater than 8 days, as well as the effect on PFS.”

Oral anticancer therapies such as ibrutinib (Imbruvica, Pharmacyclics) offer convenience to patients. However, monitoring adherence to therapy can be problematic.

Deisinger and colleagues sought to understand the relationship between adherence to ibrutinib and treatment outcomes by evaluating the effect of dose intensity and dose interruptions due to adverse events on PFS in 195 patients treated with ibrutinib in the RESONATE trial. Overall results from that trial showed ibrutinib led to more durable remissions in patients with relapsed/refractory CLL compared with ofatumumab (Arzerra, Novartis).

Deisinger and colleagues defined dose intensity as the ratio between administered ibrutinib to the planned 420-mg dose of ibrutinib. All patients began treatment with daily doses of 420 mg regardless of weight, age or comorbidities.

After a median of 8.6 months of treatment, mean ibrutinib dose intensity was 95% (median, 100%).

Seventy-six patients had a dose interruption, 73 of whom (92%) restarted treatment at standard protocol dosage.

Patients with a dose intensity above 95% experienced longer median PFS than patients whose dose intensity was below the mean (not reached vs. 6.9 months; P = 0.012).

Among patients with PFS events, 137 missed fewer than 8 days of ibrutinib and 57 had dose interruptions of at least 8 consecutive days. For patients with dose interruptions lasting longer than 8 consecutive days, the mean duration of a missed dosing event was 18.7 days.

Patients with dose interruptions of less than 8 days demonstrated long median PFS (median PFS not reached vs. 10.9 months).

These data show that a higher mean ibrutinib dose intensity leads to PFS improvements. Oncology nurses can provide patients with the necessary tools and education to adequately adhere to the full dosage of ibrutinib, Deisinger and colleagues wrote.

“It is imperative to educate our patients on the clinical importance of sustained adherence to the continuous once-daily dose of 420 mg in patients with previously treated CLL,” Deisinger said. “Because oral chemotherapy typically means fewer doctor visits, it is essential that oncology providers and nurses develop strategies to educate, assess and document oral adherence in their patients who will be administering their chemotherapy pills independently.”– by Nick Andrews

Reference :

Deisinger S, et al. Abstract 192. Presented at: ONS Annual Congress; April 28-May 1, 2016; San Antonio, Texas.

Disclosure : The study was funded in part by Pharmacyclics.