Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 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, Adrian Wiestner, 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, Adrian Wiestner
Abstract
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.
Conflict of interest statement
Conflict-of-interest disclosure: M.Z.H.F. is employed by Merck, owns stocks, and has received travel support from Merck. A.W. received research support from Pharmacyclics. N.S.S. received research support from Pharmacyclics. C.U.N. received consultancy fees and/or travel grants outside the current study from Janssen, AbbVie, Novartis, Gilead, and Roche. C.H.G. received consultancy fees from Janssen and Celgene and research support from Novo Nordisk. The remaining authors declare no competing financial interests.
© 2018 by The American Society of Hematology.
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Source: PubMed