Home Hematology and Oncology Researchers Examine Etiology of Ibrutinib Discontinuation in CLL

Researchers Examine Etiology of Ibrutinib Discontinuation in CLL

Poor prognosis after discontinuation for disease progression, especially Richter’s transformation

THURSDAY, Feb. 26, 2015 (HealthDay News) — For patients with chronic lymphocytic leukemia (CLL), the Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective, and prognosis is poor after discontinuation, according to a study published online Feb. 26 in JAMA Oncology. The research identifies, for the first time, baseline factors associated with ibrutinib therapy discontinuation.

Kami J. Maddocks, M.D., from The Ohio State University in Columbus, and colleagues examined features associated with discontinuation of ibrutinib therapy and outcomes in a cohort of 308 patients participating in four clinical trials of ibrutinib. Patients were followed for a median of 20 months.

During follow-up, the researchers found that 232 patients remained on therapy, 31 discontinued due to disease progression (including Richter’s transformation [RT] or progressive CLL), and 45 discontinued for other reasons. RT seemed to occur early (cumulative incidence at 12 months, 4.5 percent), while CLL progression appeared later (cumulative incidence at 12 months, 0.3 percent). Following RT and CLL progression, the median survival was 3.5 and 17.6 months, respectively. Sequencing on peripheral blood revealed mutations in BTK from two of eight patients with RT; deep sequencing revealed BTK or PLCG2 mutations in all 11 patients with CLL progression.

“These data show that continued clinical trials are needed in this disease and that scientific progress cannot stop even with a breakthrough drug like ibrutinib,” the authors write. “Patients with RT remain a high research priority to identify new targets and new therapies.”

Several authors disclosed financial ties to pharmaceutical companies, including Pharmacyclics, which was involved in funding some of the trials.

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