title: Plasma alemtuzumab levels in patients with chronic lymphocytic leukemia treated with alemtuzumab combined with chemotherapy reflect the efficacy of the treatment: a hypothesis.
abstract: In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Fie Juhl
authors.initials: FJ
authors.lastname: Vojdeman
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Mars
authors.initials: M
authors.lastname: van't Veer
authors.forename: Maija
authors.initials: M
authors.lastname: Itälä-Remes
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Geir Erland
authors.initials: GE
authors.lastname: Tjønnfjord
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozák
authors.forename: Aaron
authors.initials: A
authors.lastname: Polliack
authors.forename: Michela
authors.initials: M
authors.lastname: Montagna
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Nikolai
authors.initials: N
authors.lastname: Kirkby
authors.forename: Marinus
authors.initials: M
authors.lastname: van Oers
authors.forename: Christian Hartmann
authors.initials: CH
authors.lastname: Geisler
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy*; D008231:Lymphopenia / Q000139:chemically induced; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab