title: Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib.
abstract: Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse.
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Weill Cornell Medical College, New York, NY;
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.affiliation: Stanford Cancer Center and Stanford University School of Medicine, Stanford, CA;
authors.forename: Steven E
authors.initials: SE
authors.lastname: Coutre
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Burger
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
authors.affiliation: Weill Cornell Medical College, New York, NY;
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Johnson
authors.affiliation: Pharmacyclics, Inc, Sunnyvale, CA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shaw
authors.affiliation: Pharmacyclics, Inc, Sunnyvale, CA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bilotti
authors.affiliation: Pharmacyclics, Inc, Sunnyvale, CA.
authors.forename: Cathy
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Pharmacyclics, Inc, Sunnyvale, CA.
authors.forename: Danelle F
authors.initials: DF
authors.lastname: James
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010880:Piperidines; D011014:Pneumonia / Q000139:chemically induced; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine