Cardiovascular toxicities associated with ibrutinib in elderly patients.

Abstract

e15061 Background: Ibrutinib is as a first line treatment option for chronic lymphocytic leukemia/small lymphocytic lymphoma and Waldenström’s macroglobulinemia. It is also FDA approved as a subsequent therapy for mantle cell lymphoma, marginal zone lymphoma, and chronic graft versus host disease. Cardiovascular (CV) toxicities, such as atrial fibrillation (afib), are some of the most common reasons for modifying ibrutinib therapy and tend to occur within the first few months of initiation. There is currently no FDA approved recommendation to reduce the dose of ibrutinib in the elderly, despite the greater incidence of afib in this patient population. It is unclear if this increased incidence leads to subsequent treatment modification in the elderly. Thus, further review of CV toxicities amongst Kaiser Permanente members may provide evidence to offer a reduced starting dose of ibrutinib in the elderly. Methods: This retrospective, multi-center study evaluated patients who started ibrutinib between January 1, 2014 and January 1, 2020 at an FDA approved dose per indication. Patient charts were reviewed from the time of treatment initiation up to one year of treatment or death, whichever came first. Data such as demographic information, diagnosis, adverse events, and ibrutinib treatment modifications were collected from chart review. The primary objective of this study was to determine if elderly (70 years or older) patients starting ibrutinib experienced a greater incidence of CV toxicities resulting in treatment modification and/or death. CV toxicities were only included if they occurred within the first year after starting ibrutinib. Results: Of the 50 patients included in this study, 23 (46%) patients initiated ibrutinib at an elderly age (70 years or older). Three (11.1%) non-elderly and two (8.7%) elderly patients underwent treatment modifications due to CV toxicities (p=0.78). Three additional patients experienced CV toxicities without further treatment modifications. Two (one per patient group) patients had already suspended ibrutinib for hepatic and/or hematological toxicities when they experienced afib. One non-elderly patient was hospitalized for afib but continued ibrutinib as originally prescribed. Conclusions: This study did not detect a significant difference in CV toxicities between elderly and non-elderly patients. Cardiac arrhythmia rates appeared slightly higher than those reported in clinical trials, but this may be due to the smaller sample size of this study. At this time, further evidence is needed to support a lower starting dose for elderly patients on ibrutinib.