Management of Ibrutinib Failure
– Dr. Matthew Davids

The oral BTK inhibitor ibrutinib has revolutionized the treatment of patients with chronic lymphocytic leukemia (CLL), both in the relapsed and frontline settings.  Ibrutinib has shown to have a high rate of response and can induce durable remissions, even in patients with high-risk forms of CLL such as those with deletion 17p.    

Although ibrutinib is highly effective and generally well-tolerated across a number of treatment lines in CLL, increasingly patients are having to come off therapy or become resistant. Drug discontinuation is caused by a variety of reasons, including toxicity, disease progression, and Richter’s transformation. 

Several management options for patients post-ibrutinib have been identified based on evolving clinical trials data as well as clinical practice experience. Several older agents, including alemtuzumab (if marrow, blood or spleen disease is predominant), high-dose methylprednisolone (tends to work best with lymph node disease), or lenalidomide, could be considered. Novel therapeutic strategies could also be used, such as venetoclax, idelalisib, next generation BCR inhibitors, or clinical trials.