Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Blood, 2018-05, Vol.131 (21), p.2357-2366

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. Median minimal residual disease (MRD) in peripheral blood was 3.8 × 10−2 at 4 years, with MRD-negative (<10−4) 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-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733. •With 5-year median follow-up, continuous single-agent ibrutinib therapy was well tolerated with deepening of response.•Previously untreated patients, even those with TP53 aberration, achieved durable responses. [Display omitted]