Journal Article

Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation

Link, C S, Schmiedgen, M, Teipel, R, von Bonin, M, Heidenreich, F, Rücker-Braun, E, Platzbecker, U, Middeke, J M, Muetherig, A, Bornhäuser, M, Schetelig, J, Oelschlägel, U, Reinhardt, J, Trautmann-Grill, K

2016

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/1854 / 631/250/1904 / Adult / Aged / Bone marrow / Bruton's tyrosine kinase / Care and treatment / CD4 antigen / Cell Biology / Chronic lymphocytic leukemia / Cytokines / Enzyme inhibitors / Evaluation / Female / Flow cytometry / Graft-versus-host reaction / Helper cells / Hematology / Humans / Ibrutinib / Immunomodulation / Inhibitor drugs / Interleukin 1 / Interleukin 10 / Internal Medicine / Kinases / Leukemia, Lymphocytic, Chronic, B-Cell - complications / Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy / Leukemia, Lymphocytic, Chronic, B-Cell - therapy / Lymphocytes / Lymphocytes T / Male / Medicine / Medicine & Public Health / Methods / Middle Aged / Minimal residual disease / Neutropenia - chemically induced / original-article / Patient outcomes / Patients / Protein-tyrosine kinase / Public Health / Pyrazoles - administration & dosage / Pyrazoles - adverse effects / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Recurrence (Disease) / Remission / Retrospective Studies / Salvage Therapy - methods / Stem cell transplantation / Stem Cells / Transplantation / Treatment Outcome / Tumor necrosis factor-α / Tyrosine