Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib

Abstract

Ibrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of patients with relapsed refractory chronic lymphocytic leukemia (RR-CLL). We describe the characteristics, causes of discontinuation, and outcomes in patients who discontinued treatment with ibrutinib. One hundred twenty-seven patients were enrolled in various clinical trials of ibrutinib, with or without rituximab, at our center. Thirty-three (26%) patients have discontinued ibrutinib to date. The majority of those patients had high-risk features: 94% with unmutated immunoglobulin heavy chain variable gene rearrangement, 58% with del(17p) by fluorescence in situ hybridization, and 54% with a complex karyotype. Causes of discontinuation were disease transformation (7), progressive CLL (7), stem cell transplantation (3), adverse events (11), serious adverse events/deaths (3), and miscellaneous reasons (2). Twenty five patients (76%) died after discontinuing ibrutinib; the median overall survival was 3.1 months after discontinuation. Most patients with RR-CLL who discontinued ibrutinib early were difficult to treat and had poor outcomes.

Figure 1

Survival of patients after discontinuation of ibrutinib. Patients survived for a median of 3.1 months after discontinuation of ibrutinib (n = 33).

Figure 2

Postibrutinib survival of patients who progressed (without transformation; n = 7) vs those who transformed (n = 7). Median survival in patients who progressed (untransformed) was not reached vs 2.6 months in those who transformed (P = .44).