ASH Annual Meeting 'Press Program' and 'Best of ASH' Oral Presentation Abstract 189: The Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib Promotes High Response Rate, Durable Remissions, and Is Tolerable in Treatment Naïve (TN) and Relapsed or Refractory (RR) CLL or SLL Patients Including Patients with High-Risk (HR) Disease: New and Updated Results of 116 Patients in a Phase Ib/II Study John C. Byrd, M.D., The Ohio State University, Columbus, OHA multicenter, open-label, single agent Phase Ib/II study of ibrutinib in subjects with CLL/SLL either relapsed/refractory or treatment-naive (65 years of age or older). This study, which completed enrollment in July 2011 with 116 patients (31 patients treatment naive and 85 patients relapsed-refractory/high-risk patients) treated with ibrutinib monotherapy, was designed to assess safety, tolerability, and efficacy of ibrutinib at two dose levels. With a maximum follow up of 26 months, it was estimated that 96% of the treatment-naive and 75% of the relapsed-refractory/high-risk patients are without progression. Responses were independent of high risk clinical genetic features. Continuous dosing was well tolerated with a reported lack of detrimental impact on immunoglobulins or hematologic parameters. Most adverse events were Grade 2 or less in severity, with the most common being diarrhea, fatigue, upper respiratory tract infection, rash, nausea and arthralgias (joint pain). The majority of events were managed with over the counter medicines and outpatient care. Hematologic events potentially related to ibrutinib were relatively infrequent.
ASH Annual Meeting 'Press Program' and 'Best of ASH' Oral Presentation Abstract 187 The Btk inhibitor Ibrutinib in combination with rituximab is well tolerated and displays profound activity in high-risk Chronic Lymphocytic Leukemia (CLL) patients Jan A Burger, M.D., Ph.D., MD Anderson Cancer Center, Houston, TX This presentation was based on findings from a Phase 2, single-center trial with 40 high risk CLL patients treated with 420 mg/day ibrutinib in combination with rituximab, an anti-CD20 monoclonal antibody. The high risk patients had one of the following characteristics, all predictive of poor outcome to standard chemotherapy: deletion in chromosome 17p, mutation in the tumor suppressor gene TP53, deletion in chromosome 11q or relapse less than 36 months after chemo-immunotherapy. The results after a median follow-up of 4.8 months were profound in these high-risk patients, with an overall response rate of 83%. Treatment was well tolerated, with grade 3/4 adverse events reported in 13 cases that were largely unrelated to ibrutinib or the combination and transient, such as neutropenia (low white blood cell count), fatigue, pneumonia, insomnia, and bone aches.
In addition to the updates presented at ASH, Pharmacyclics and its partner Janssen Biotech recently announced the following clinical trials of ibrutinib: