Outcomes worse for CLL patients who discontinue ibrutinib after disease transformation

Patients with chronic lymphocytic leukemia who discontinued ibrutinib treatment after disease transformation had especially poor outcomes compared with those who experienced disease progression, study data showed.

Effective salvage treatments were important for patients with CLL who experienced disease progression while on ibrutinib, the researchers wrote.

“Several studies have demonstrated that from 10% to 20% of patients who receive ibrutinib discontinue therapy after a median follow-up of 1 year because of either intolerance, disease progression, transformation, or other causes,” Preetesh Jain, MBBS, MD, PhD, of the department of leukemia at the University of Texas MD Anderson Cancer Center, and colleagues wrote. “Ibrutinib resistance is a growing concern as more patients receive this treatment.”

To determine long-term outcomes, Jain and colleagues performed a retrospective analysis of 320 patients with CLL who participated in ibrutinib clinical studies at the MD Anderson Cancer Center between 2010 and 2015.

Ninety patients (28%) discontinued ibrutinib, including 80 with relapsed or refractory disease, and 10 who were treatment-naïve.

At a median follow-up of 38 months from the start of ibrutinib treatment, 40 of the 90 patients who discontinued ibrutinib (44%) remained alive.

Overall median time to discontinuation was 15 months (range, 1.2-54).

The main reasons for discontinuing ibrutinib were intolerance (32%), progression (21%), Richter transformation (10%) and miscellaneous (31%).

Median survival was 33 months for patients with ibrutinib intolerance, 16 months for progression, 2 months for Richter transformation and 11 months for miscellaneous causes.

“As the use of ibrutinib treatment continues to increase in patients with CLL, it is essential to delineate the pattern of mutation and dynamics of clonal evolution in those patients who discontinue ibrutinib because of disease progression/transformation and to identify pathways for therapeutic targeting to improve the survival outcomes for these patients,” the researchers wrote. – by Andy Polhamus

Disclosure: Jain reports no relevant financial disclosures. Please see the study for a full list of all other authors’ relevant financial disclosures.

Editor’s Note: On May 2, we corrected the text of this article to clarify that the researchers reported 40 of 90 patients (44%) who discontinued ibrutinib survived at a median 38 months of follow-up. The Editors regret this error.