Overcoming Ibrutinib Resitance In Relapsed Chronic Lymphocytic Leukemia

Resistance to ibrutinib (PCI-32765) is uncommon and not well described. Here we describe a 78 year old Caucasian man with a long standing history of CLL originally diagnosed in 2004. He was treated at the James Cancer Hospital and Fellow Research Institute at the Ohio State University since that time and received multiple regimens including fludarabine and Rituxan based regimens under the care of John Byrd, MD. He progressed and more recently was on the clinical trial of ibrutinib for relapsed CLL, which he tolerated well and to which he had an excellent response for nearly 2 years. The patient developed resistance to ibrutinib and was taken off study. According to Dr. Byrd, DNA sequencing revealed a V600 mutation (personal communication). The patient was subsequently enrolled on a clinical trial of carfilzomib, to which he did not respond and developed increasing leukocytosis with increasing numbers of prolymphocytes and transformation to B-cell PLL. He was treated with single agent ofatumumab with transient responses and rapid regrowth. He was then referred to the clinic at the Penn State Hershey State College satellite facility for care closer to his home.