title: Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia.
abstract: Background:Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or withTP53mutations. 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.Experimental Design: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.Results: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 (n= 21, 32.3 months,P= 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.Conclusions: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.Clin Cancer Res; 23(9); 2154-8. ©2016 AACR.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Internal Medicine, University of Texas, Houston.
authors: Preetesh
authors: P
authors: Jain
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Michael J
authors: MJ
authors: Keating
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: William G
authors: WG
authors: Wierda
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Mariela
authors: M
authors: Sivina
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Philip A
authors: PA
authors: Thompson
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Zeev
authors: Z
authors: Estrov
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Hagop
authors: H
authors: Kantarjian
authors: Chao Family Comprehensive Cancer Center, UC Irvine, Orange, California.
authors: Susan
authors: S
authors: O'Brien
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas. jaburger@mdanderson.org.
authors: Jan A
authors: JA
authors: Burger
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000069283:Rituximab; D000225:Adenine