Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study

作者：Ahn, Inhye E.; Farooqui, Mohammed Z. H.; Tian, Xin; Valdez, Janet; Sun, Clare; Soto, Susan; Lotter, Jennifer; Housel, Stephanie; Stetler-Stevenson, Maryalice; Yuan, Constance M.; Maric, Irina; Calvo, Katherine R.; Nierman, Pia; Hughes, Thomas E.; Saba, Nakhle S.; Marti, Gerald E.; Pittaluga, Stefania; Herman, Sarah E. M.; Niemann, Carsten U.; Pedersen, Lone B.; Geisler, Christian H.; Childs, Richard; Aue, Georg; Wiestner, Adrian^*

来源：Blood, 2018, 131(21): 2357-2366.

DOI：10.1182/blood-2017-12-820910

• CHRONIC LYMPHOCYTIC-LEUKEMIA
• PREVIOUSLY UNTREATED PATIENTS
• SINGLE-AGENT IBRUTINIB
• OPEN-LABEL
• CLONAL EVOLUTION
• 17P DELETION
• TUMOR PROLIFERATION
• BTK INHIBITION
• TRIAL
• RESISTANCE

The safety and efficacy of ibrutinib (420 mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase 2 study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled because of age 65 years or older (elderly cohort). Both cohorts included patients with treatment-naive (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20.9%) patients for a rate of 6.4 per 100 patient-years. No serious bleeding occurred. The overall response rate at 6 months, the primary study endpoint, was 95.8% for the TP53 cohort (95% confidence interval, 85.7%-99.5%) and 93.9% for the elderly cohort (95% confidence interval, 79.8%-99.3%). Depth of response improved with time: at best response, 14 (29.2%) of 48 patients in the TP53 cohort and 9 (27.3%) of 33 in the elderly cohort achieved a complete response. Medianminimal residual disease (MRD) in peripheral blood was 3.8 3 1022 at 4 years, with MRD-negative (< 1024) remissions in 5 (10.2%) patients. In the TP53 cohort, the estimated 5-year progression-free survival (PFS) was 74.4% in TN-CLL compared with 19.4% in RR-CLL (P=.0002), and overall survival (OS) was 85.3% vs 53.7%, respectively (P=.023). In the elderly cohort, the estimated 5-year PFS and OS in RR-CLL were 64.8% and 71.6%, respectively, and no event occurred in TN-CLL. Long-termadministration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733.

• 出版日期2018-5-24