According to a study published in JAMA Oncology, approximately 10% of patients with chronic lymphocytic leukemia (CLL) discontinued therapy with the Bruton tyrosine kinase inhibitor ibrutinib owing to disease progression during clinical trials.
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is considered incurable without an allogeneic stem cell transplant. However, some therapeutic advances have been made, notably with the emergence of kinase inhibitors for patients with disease relapse.
Bruton’s tyrosine kinase is a protein that is essential for the survival and proliferation of CLL cells, and ibrutinib (approved by the US FDA in CLL and mantle cell lymphoma) is the first drug designed to target this protein.
Centered on four trials at The Ohio State University Comprehensive Cancer Center–Arthur G James Cancer Hospital and Richard J Solove Research Institute (OH, USA), the present study reports the characteristics of 308 patients who discontinued ibrutinib therapy and their outcomes.
The findings indicate that, with a median follow-up of 20 months, 232 patients (75%) remained on ibrutinib therapy, 31 (10%) discontinued therapy owing to disease progression and 45 (15%) discontinued therapy due to other reasons. Disease progression included Richter’s transformation (which appeared to occur early) or progressive CLL (which appeared later); the results indicated that median survival was 3.5 months after Richter’s transformation and 17.6 months following CLL progression.
“These data enhance our understanding of how patients do on ibrutinib long term and who is likely to relapse. We know that many patients will have very durable remissions with ibrutinib, and understanding which patients are at higher risk helps us select who might benefit from clinical trials investigating other new agents and combination therapies rather than starting ibrutinib treatment by itself,” commented hematologist and study author Jennifer Woyach (The Ohio State University Comprehensive Cancer Center). “We have confirmed that specific gene mutations are seen in patients who relapse, which gives us an idea of other drugs that might be effective in these circumstances.”
The study concludes that ibrutinib is an effective therapy for CLL and for the first time identifies baseline factors associated with ibrutinib therapy discontinuation.
“Outcomes data show poor prognosis after discontinuation, especially for those patients with Richter’s transformation. Patients with either progressive CLL or Richter’s tend to require therapy quickly after ibrutinib is stopped, so having a plan in place for alternative therapy is necessary. This sub-segment of patients who relapse on ibrutinib remains a high research priority to identify new targets and new therapies, and we have multiple studies ongoing at the James to try to help these patients,” commented coauthor Kami Maddocks (The Ohio State University Comprehensive Cancer Center).