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Clinical Trial
. 2017 Mar 1;23(5):1149-1155.
doi: 10.1158/1078-0432.CCR-16-1431. Epub 2017 Jan 10.

Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Steven E Coutré  1 , Richard R Furman  2 , Ian W Flinn  3 , Jan A Burger  4 , Kristie Blum  5 , Jeff Sharman  6 , Jeffrey Jones  5 , William Wierda  4 , Weiqiang Zhao  5 , Nyla A Heerema  5 , Amy J Johnson  5 , Anh Tran  7 , Cathy Zhou  7 , Elizabeth Bilotti  7 , Danelle F James  7 , John C Byrd  5 , Susan O'Brien  4
Affiliations
Clinical Trial

Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Steven E Coutré et al. Clin Cancer Res. .

Abstract

Purpose: Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase Ib/II study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL.Experimental Design: We report data with 44 months of follow-up on 94 patients with TN and R/R CLL/SLL receiving ibrutinib 420 mg once-daily in PCYC-1102 and the long-term extension study PCYC-1103.Results: Ninety-four CLL/SLL patients (27 TN, 67 R/R) were treated with ibrutinib (420 mg/day). Patients with R/R disease had received a median of four prior therapies (range, 1-12). Responses were rapid and durable and median duration of response was not reached. Best overall response was 91% [85% TN (complete response, CR 26%) and 94% R/R (9% CR)]. Median progression-free survival (PFS) was not reached in either group. The 30-month PFS rate was 96% and 76% for TN and R/R patients, respectively. Ibrutinib was well tolerated with extended follow-up; rates of grade ≥3 cytopenias and fatigue, as well as discontinuations due to toxicities decreased over time.Conclusions: Single-agent ibrutinib at 420 mg once-daily resulted in durable responses and was well tolerated with up to 44 months follow-up in patients with TN and R/R CLL/SLL. Currently, 66% of patients continue on ibrutinib. Clin Cancer Res; 23(5); 1149-55. ©2017 AACR.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest: SEC has been engaged in a consulting or advisory role for Janssen and Pharmacyclics and received research funding from AbbVie and Pharmacyclics; RRF has received honoraria, has been engaged in a consulting or advisory role, and has been a member of a speakers’ bureau for Pharmacyclics; IWF received research funding from Pharmacyclics and Janssen; JB has been engaged in a consulting or advisory role for Janssen, Boehringer Ingelheim, and Portola, received research funding from Pharmacyclics and Gilead, and received travel or accommodation reimbursement from Roche and Janssen; KB received research funding from Celgene, Novartis, Janssen, Pharmacyclics, Seattle Genetics, Millennium, Gilead, MorphoSys, and Constellation Pharmaceuticals; JS received honoraria from and has been engaged in a consulting or advisory role with Pharmacyclics, received research funding from Pharmacyclics, Gilead, and Janssen, and is a member of speakers’ bureau for Gilead; JJ has been engaged in a consulting or advisory role with Pharmacyclics and received research funding from Pharmacyclics and AbbVie; WW received honoraria from and has been engaged in a consulting or advisory role for Sanofi, Genentech/Roche, Pharmacyclics, Celgene, Gilead, GSK/Novartis, Genzyme, Merck, AbbVie, and Emergent and received research funding from GSK/Novartis, AbbVie, Karyopharm, Genentech, Pharmacyclics, Acerta, Gilead, Janssen, Emergent, Juno, and Kite; AT, CZ, EB, and DFJ declare employment by and ownership interest in Pharmacyclics; SO has received honoraria and research funding from and has been engaged in a consulting or advisory role for Pharmacyclics. WZ, NAH, AJJ, and JCB declare no competing financial interests.

Figures

Figure 1.
Figure 1.. Grade ≥3 adverse events.
(A) Grade ≥3 adverse events by time to event onset. Listed adverse events include those that occurred in ≥5% of patients in all-treated population; denominator for each term and time period can vary based on those at risk. (B) Frequency of grade ≥3 adverse events by treatment-naïve (TN) or relapsed/refractory (R/R) status.
Figure 2.
Figure 2.. Best response by investigator assessment and survival with ibrutinib over time.
(A) Best response (investigator-assessed) to ibrutinib therapy. (B) Progression-free and (C) overall survival in patients with TN and R/R CLL.
Figure 3.
Figure 3.. Change in blood cell counts over time.
(A) Mean hemoglobin levels and platelet counts over time among all patients receiving ibrutinib 420 mg/day with baseline anemia (defined as baseline hemoglobin ≤110 g/L) or thrombocytopenia (defined as baseline platelets ≤100 × 109/L). (B) Change in white blood cell differential and in absolute numbers of white blood cells over time.
See this image and copyright information in PMC

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