Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies
University of Vermont · The University of Texas MD Anderson Cancer Center · +8 more institutions
Abstract
Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months.
Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.
Citation impact
- FWCI
- 57.61
- Percentile
- 100%
- References
- 32
Authors
15- RHRanjana H. AdvaniCorresponding
University of Vermont, The University of Texas MD Anderson Cancer Center, Willamette University, Cornell University, University of Chicago, Sunnyvale Public Library, Joint Center for Structural Genomics, Stanford Medicine, Nebraska Cancer Specialists, Stanford University
- JJJoseph J. Buggy
University of Vermont, The University of Texas MD Anderson Cancer Center, Willamette University, Cornell University, University of Chicago, Sunnyvale Public Library, Joint Center for Structural Genomics, Stanford Medicine, Nebraska Cancer Specialists, Stanford University
- JPJeff P. Sharman
University of Vermont, The University of Texas MD Anderson Cancer Center, Willamette University, Cornell University, University of Chicago, Sunnyvale Public Library, Joint Center for Structural Genomics, Stanford Medicine, Nebraska Cancer Specialists, Stanford University
- SMSonali M. Smith
University of Vermont, The University of Texas MD Anderson Cancer Center, Willamette University, Cornell University, University of Chicago, Sunnyvale Public Library, Joint Center for Structural Genomics, Stanford Medicine, Nebraska Cancer Specialists, Stanford University
- TEThomas E. Boyd
University of Vermont, The University of Texas MD Anderson Cancer Center, Willamette University, Cornell University, University of Chicago, Sunnyvale Public Library, Joint Center for Structural Genomics, Stanford Medicine, Nebraska Cancer Specialists, Stanford University
Topics & keywords
- Ibrutinib
- Bruton's tyrosine kinase
- Medicine
- Dosing
- Chronic lymphocytic leukemia
- Pharmacology
- Tyrosine-kinase inhibitor
- Internal medicine
- Good health and well-being