Incidence and description of autoimmune cytopenias during treatment with ibrutinib for chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AICs). Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase approved for the treatment of relapsed CLL and CLL with del(17p). The effect of ibrutinib treatment on the incidence of AIC is currently unknown. We reviewed medical records of 301 patients treated with ibrutinib, as participants in therapeutic clinical trials at The Ohio State University Comprehensive Cancer Center between July 2010 and July 2014. Subjects were reviewed with respect to past history of AIC, and treatment-emergent AIC cases were identified. Before starting ibrutinib treatment, 26% of patients had experienced AIC. Information was available for a total of 468 patient-years of ibrutinib exposure, during which there were six cases of treatment-emergent AIC. This corresponds to an estimated incidence rate of 13 episodes for every 1000 patient-years of ibrutinib treatment. We further identified 22 patients receiving therapy for AIC at the time ibrutinib was started. Of these 22 patients, 19 were able to discontinue AIC therapy. We found that ibrutinib treatment is associated with a low rate of treatment-emergent AIC. Patients with an existing AIC have been successfully treated with ibrutinib and subsequently discontinued AIC therapy.

Conflict of interest statement

Conflict of Interest

The authors would like to disclose conflicts of interest. Dr. Jones has served as a consultant for Pharmacyclics and Janssen. Dr. Maddocks has received research support from Pharmacyclics. Dr. Blum has received research funding from Pharmacyclics and Janssen. Dr. Jaglowski has received research funding and has served as a consultant for Pharmacyclics. All other authors declare no competing interests.

Figures

Figure 1. Relationship of AIC episodes and therapy to ibrutinib treatment

Time from the start of most recent AIC therapy to AIC therapy discontinuation is shown for the 22 patients who were on a continuous AIC therapy at the time of starting ibrutinib. All AIC episodes experienced by these patients are shown. Two patients were censored when they were no longer followed for their AIC therapy. One patient was censored at last follow up when known to be taking prednisone. * Episode of AIHA treated with steroids, with a second episode after ibrutinib was discontinued. ** Episode of ITP treated with IVIG.