Long-term ibrutinib yields good depth and duration of response among patients with chronic lymphocytic leukemia (CLL) regardless of TP53 status, according to a study published in Blood.1
Chemoimmunotherapy — the current standard of care for CLL — leads to high rates of remission but patients still face many challenges, including a high rate of relapse (particularly among those with TP53 mutations) and dose-limiting toxicities that reduce the effectiveness of treatment. Previous studies suggested that ibrutinib may be a therapeutic alternative.
For this open-label phase 2 study (ClinicalTrials.gov Identifier: NCT01500733), researchers enrolled 86 patients with CLL regardless of treatment history to receive ibrutinib 420 mg once daily. Patients were enrolled into a TP53 aberration cohort (51 patients) or an elderly patient cohort (35 participants).
After a median follow-up of 4.8 years, 57% of patients remained in the study: 23.3% and 5.8% of patients discontinued treatment because of progressive disease and adverse events, respectively.
The overall response rate at 6 months in the TP53 cohort was 95.8% (95% CI, 85.7%-99.5%) and 93.9% (95% CI, 79.8%-99.3%) in the elderly patient cohort. Response to treatment deepened over time: 29.2% of patients in the TP53 cohort and 27.3% of patients in the elderly cohort had a complete response. At 4 years, minimum residual disease (MRD) in peripheral blood was 3.8×10-2, and 8.3% of patients had MRD negative (< 10-4) remission.
In the TP53 cohort, the estimated 5-year progression-free survival (PFS) rate was 74.4% among treatment-naive patients vs 19.4% among patients with relapsed/refractory disease (P = .0002). In the elderly cohort, the 5-year PFS rate was 64.8% among patients with relapsed/refractory disease.
The 5-year overall survival (OS) rate was 85.3% among treatment-naive patients vs 53.7% among patients with relapsed/refractory disease (P = .023) in the TP53 cohort. The 5-year OS rate was 71.6% among elderly patients with relapsed/refractory disease.
No PFS or OS events were reported for treatment-naive elderly patients.
The safety profile remained consistent with previous findings. Most adverse events (AE) were transient and limited to grade 1 or 2. The most frequently observed grade 3 or worse AEs were infection (9.3%) and atrial fibrillation (5.8%).
- Ahn IE, Farooqui MZ, Tian X, et al. Depth and durability of response to ibrutinib in CLL: 5-year follow-up of phase II study. Blood. 2018 Feb 26. doi: 10.1182/blood-2017-12-820910 [Epub ahead of print]