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

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

Key points

  • With 5 years 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.


Safety and efficacy of ibrutinib (420mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase II study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled for age ≥ 65 years (elderly cohort). Both cohorts included patients with treatment-naïve (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% CI, 85.7-99.5) and 93.9% in the elderly cohort (95% CI, 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 3.8x10-2 at 4 years, with MRD negative (<10-4) remissions in 5 (8.3%) patients. In the TP53 cohort, the estimated 5-year progression-free survival (PFS) was 74.4% in TN-CLL compared to 19.4% in RR-CLL (P=.0002), and overall survival (OS) was 85.3% versus 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, while no event occurred in TN-CLL. Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. #NCT01500733.

  • Submitted December 7, 2017.
  • Accepted February 14, 2018.