Introduction: Recent randomized trials have demonstrated the efficacy of ibrutinib-based therapy in the treatment of patients with CLL. In Alliance A041202, a higher than expected number of unexplained deaths were reported with front-line ibrutinib in a patient population aged at least 65 years compared to ECOG 1912, which included patients up to 70 years of age.
Methods: Therefore, we conducted a retrospective analysis to investigate whether ibrutinib was associated with a greater mortality in older patients outside of a clinical trial setting. This multicenter analysis was performed by investigators at 20 academic and community practices.
Results: Amongst the 391 patients included, there was no correlation between age and response rate, PFS, or OS. However, there was a trend to higher rate of deaths in patients > 65-years-old (8.7% vs 3.8%, p=0.097), with an increased number of early deaths (13 vs 4, p=0.3).
Conclusion: These data suggest greater intolerance, and possibly mortality, with ibrutinib in an older population. Patients should be educated regarding the potential complications related to ibrutinib and symptoms of concern to report.


Keywords: CLL, ibrutinib, elderly


INTRODUCTION

Recently published cooperative group studies, Alliance A041202 and ECOG E1912, have established the role of ibrutinib over chemoimmunotherapy for the front-line treatment of chronic lymphocytic leukemia (CLL).1,2 Notably, Alliance A041202, which evaluated patients ≥65-years-old receiving ibrutinib with or without rituximab or the combination of bendamustine and rituximab (BR), reported a higher than expected number of deaths in both of the ibrutinib-containing arms.1 Ten unexplained/unknown deaths occurred among the 361 patients receiving ibrutinib; whereas 1 such event occurred in the BR arm (n=176). These data were in contrast to ECOG E1912 in which ibrutinib plus rituximab was associated with an improvement in overall survival (OS) compared to FCR (fludarabine, cyclophosphamide, rituximab) in patients less than 70 years of age.2 Together, these data suggest ibrutinib may be associated with significant adverse events (AE) and greater mortality in an elderly CLL population. We sought to investigate this hypothesis in previously untreated patients who received commercially available ibrutinib as initial therapy for CLL.

METHODS

This multicenter retrospective analysis was performed by investigators at 20 academic and community practices. The study was approved by the institutional review board at each participating institution. Informed consent was waived because the research involved no more than minimal risk to the patient. In compliance with the Declaration of Helsinki, patient confidentiality was maintained through de-identified data collection practices. Patients were considered eligible for inclusion if they received ibrutinib for the front-line treatment of CLL through commercial sources. Medical chart review via diagnostic codes was performed to identify all CLL patients at each institution. Investigators utilized chart review, electronic medical records, and related databases to obtain required information. Patient demographics, prognostic markers, ibrutinib dosing administration, and clinical outcomes data were collected. The International Workshop on Chronic Lymphocytic Leukemia (iwCLL, 2008) criteria were used to define response and progression of disease.3


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