title: Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.
abstract: Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|DFG Research Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: C S
authors.initials: CS
authors.lastname: Link
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Teipel
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Heidenreich
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Rücker-Braun
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmiedgen
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Reinhardt
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Oelschlägel
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Bonin
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Middeke
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Muetherig
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Trautmann-Grill
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|DFG Research Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|DKMS Clinical Trials Unit, Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schetelig
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010880:Piperidines; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine