title: Modeling absolute lymphocyte counts after treatment of chronic lymphocytic leukemia with ibrutinib.
abstract: The objective in this study was to characterize the pattern of the treatment-related lymphocytosis curve in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and assess the relationship between the baseline factors and absolute lymphocyte counts (ALC). The PCYC-1102-CA study was a five-arm phase Ib/II open-label, nonrandomized, multicenter study in CLL/SLL. The arms and accruals were 420 and 840 mg/day treatment-naive elderly CLL/SLL (N = 27 and N = 4, respectively), 420 and 840 mg/day relapsed/refractory CLL/SLL (N = 27 and N = 34, respectively), and 420 mg/day high-risk CLL/SLL (N = 24). The results were generated through statistical modeling using data from a clinical trial (PCYC-1102) in five cohorts of treatment-naïve or relapsed/refractory CLL patients treated at 420 and 840 mg daily of ibrutinib. In cases in which the initial increase in ALC doubles by day 28, it takes patients longer to reach their maximum ALC when compared with those with a lower rate of increase. Our models show that all of the cohorts exhibited the same pattern of treatment-related lymphocytosis from ibrutinib, and there are no significant differences between cohorts, including no detectable dose effect. The ALC of the majority of patients return to baseline ALC values by the end of cycle 5.
authors.affiliation: Division of Biostatistics, 1500 E Duarte Rd, City of Hope, Duarte, CA, 91010-3000, USA, dsmith02@coh.org.
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.forename: Leanne
authors.initials: L
authors.lastname: Goldstein
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.forename: Danelle F
authors.initials: DF
authors.lastname: James
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kunkel
authors.forename: Maria
authors.initials: M
authors.lastname: Fardis
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hamdy
authors.forename: Raquel
authors.initials: R
authors.lastname: Izumi
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Buggy
authors.forename: Fong
authors.initials: F
authors.lastname: Clow
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy*; D016014:Linear Models; D018655:Lymphocyte Count; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D010880:Piperidines; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine