Led by Farooqui and colleagues, this investigator-initiated phase 2, single-center trial of ibrutinib monotherapy prospectively evaluated the role of ibrutinib in patients with chronic lymphocytic leukemia (CLL), with and without deletion 17p. The primary end point of the study was response after 6 months as assessed by computed tomography, bone marrow biopsy, and routine clinical and laboratory studies. Farooqui and colleagues reported on the first 53 patients (29 patients with deletion 17p, 24 patients without deletion 17p) after a median follow-up of 14 months.
The estimated event-free survival at 14 months was 93%. At 6 months, 66% of patients achieved partial response (PR), as defined by the International Workshop on CLL criteria, and 28% of patients achieved PR with lymphocytosis. Responses by treatment cohort are shown in Figure 1. The apparent difference in response rates was because of slower clearance of the treatment-induced lymphocytosis in patients with deletion 17p. Clinical benefit and disease control in all tissue sites were equal for patients with and without deletion 17p (Figure 2).
PD indicates progressive disease; PR, partial response; SD, stable disease.
To obtain a direct measure of the relative impact of ibrutinib on tumor cells carrying deletion 17p, Farooqui repeated chromosome testing at 6 months in 20 patients. In these patients, deletion 17p was present in 12% to 97% of tumor cells prior to treatment with ibrutinib and in 0% to 92% of tumor cells after 6 months of ibrutinib therapy. Of note, in 80% of patients, the relative size of the deletion 17p subclone decreased, and 4 patients had no evidence of the deletion 17p subclone after 6 months.
Most adverse events (AEs) were grade 2 or lower and included diarrhea, fatigue, arthralgia, myalgia, and rash. Grade 3 or higher infections or cytopenia were reported in 15% of patients, regardless of causality. Of note, 4 deaths that occurred during the study period were not related to the treatment.
Farooqui and colleagues concluded that single-agent ibrutinib was equally effective against CLL in patients with or without deletion 17p.
Farooqui M, Aue G, Valdez J, et al. Single agent ibrutinib (pci-32765) achieves equally good and durable responses in chronic lymphocytic leukemia (CLL) patients with and without deletion 17p. Blood. 2013;122(21). Abstract 673.