Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia.

Abstract

<b>Background:</b> Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with <i>TP53</i> mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial.<b>Experimental Design:</b> We report the long-term outcome [median follow-up of 47 months (range, 36-51 months)] of 40 patients with high-risk CLL, treated on the first ibrutinib combination trial with rituximab (IR). The majority of patients (36/40) were previously treated.<b>Results:</b> Median age was 65 years, and 21 patients (52%) had 17p deletion. Median duration on treatment was 41 months (range, 2-51 months), and median number of treatment cycles was 42 (range, 2-49). Overall response rate was 95%, and 9 patients (23%) attained a complete remission. Twenty-one patients discontinued treatment, 10 due to disease progression, 9 for other causes, and 2 due to stem cell transplantation; the remaining 19 patients continue on ibrutinib. Median progression-free survival for all patients was 45 months, which was significantly shorter in the subgroup of patients with del17p (<i>n</i> = 21, 32.3 months, <i>P</i> = 0.02). Fourteen patients (35%) died, five from progressive disease, five from infections, and four from other causes. Median overall survival has not been reached.<b>Conclusions:</b> IR combination therapy leads to durable remissions in high-risk CLL; the possible benefit from the addition of rituximab is currently explored in a randomized trial. <i>Clin Cancer Res; 23(9); 2154-8. ©2016 AACR</i>.