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The Bruton’s Tyrosine Inhibitor Ibrutinib (PCI-32765) Monotherapy Demonstrates Long-Term Safety and Durability of Response in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in an Open-Label Extension Study

Conference Correspondent - Conference Highlights ASH

Bruton’s tyrosine kinase (BTK) plays a critical role in chronic lymphocytic leukemia (CLL) cell survival by modulating B-cell receptor signaling. Ibrutinib, a first-in-class oral inhibitor of BTK that was recently approved for use in mantle cell lymphoma, has been shown to inhibit proliferation, migration, and adhesion in CLL cells.1

In an open-label extension study conducted by O’Brien and colleagues, a total of 148 patients with CLL/small lymphocytic lymphoma (SLL) received ibrutinib monotherapy in a phase 1 study (PCYC-04753) or a phase 1b/2 study (PCYC-1102-CA), after which enrollment in a long-term extension study was offered.2 The extension study allowed continued follow-up for safety and efficacy with daily orally administered ibrutinib monotherapy. Patients who were included in the study had either untreated or relapsed or refractory CLL/SLL. The goals of the present analysis were to evaluate the safety of ibrutinib therapy over time (≤ 1 year and > 1 year), summarize safety findings in patients with untreated or relapsed or refractory CLL, and assess duration of response to ibrutinib.2

After a median treatment duration of 21.5 months, 109 of 148 patients continued treatment with ibrutinib for more than a year.  The percent of patients who had grade 3 or higher serious adverse events (AE) declined over time from 43% within the first year of study treatment to 32% after the first year of treatment. The number of grade 3 AEs and serious AEs determined to be related to ibrutinib therapy also declined from within the first year of treatment (24% and 8%, respectively) to after the first year of treatment (7% and 0%, respectively).2

The most frequent grade 3 or higher AEs included pneumonia, hypertension, neutropenia, thrombocytopenia, and diarrhea, regardless of causality to ibrutinib. The AEs leading to ibrutinib discontinuation occurred in 12 of 148 patients within the first year of treatment and in 6 of 109 patients after the first year of treatment. Of note, grade 3 or higher serious AEs were reported at a 2-fold higher rate in patients who had received previous therapies, which may reflect the patients’ disease state rather than AEs’ relationship to ibrutinib.2

Of the 140 patients evaluable for efficacy, 86% with untreated CLL and 88% with relapsed or refractory CLL achieved a partial response (PR) or better. When those patients who achieved PR with lymphocytosis were included, 93% of patients with untreated disease and 94% of patients with relapsed or refractory disease achieved an objective response to ibrutinib therapy.2

For patients who achieved PR or better, the median duration of response has not been reached after a median follow-up of 27 months. At 30 months, 76% of patients who responded to ibrutinib treatment were alive without disease progression.2

O'Brien and colleagues concluded that this ongoing extension study of single-agent ibrutinib demonstrates long-term safety, tolerability, and durability of response in patients with untreated or relapsed or refractory CLL/SLL.2


  1. Wilson WH, Gerecitano JF, Goy A, et al. The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the ABC subtype of relapsed/refractory de novo diffuse large B-cell lymphoma (DLBCL): interim results of a multicenter, open-label, phase study. Blood. 2012;120. Abstract 686.
  2. O'Brien S, Furman R, Fowler N, et al. The bruton’s tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765) monotherapy demonstrates long-term safety and durability of response in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in an open-label extension study. Blood. 2013;122(21). Abstract 4163.
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Last modified: August 30, 2021