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Proteasome inhibitors and IMiDs can overcome some high‐risk cytogenetics in multiple myeloma but not gain 1q21
Authors:Hareth Nahi  Thea Kristin Våtsveen  Johan Lund  Bart M.S. Heeg  Birgitte Preiss  Evren Alici  Michael Boe Møller  Karin Fahl Wader  Hanne E.H. Møller  Lill Anny Grøseth  Brian Østergaard  Hong Yan Dai  Erik Holmberg  Gösta Gahrton  Niels Abildgaard
Affiliation:1. Department of Medicine, Karolinska Institutet, Stockholm, Sweden;2. KG Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway;3. Department of Pathology, St Olavs Hospital, Trondheim, Norway;4. PharmacoEpidemiology & PharmacoEconomics (PE2), University of Groningen, Groningen, The Netherlands;5. Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands;6. Department of Pathology, Odense University Hospital, Odense, Denmark;7. Department of Oncology, St Olavs Hospital, Trondheim, Norway;8. Department of Hematology, St Olavs Hospital, Trondheim, Norway;9. Department of Hematology, Odense University Hospital, Odense, Denmark;10. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Abstract:Chromosomal aberrations have significant prognostic importance in multiple myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome the poor prognostic impact of some of them. In this study, we investigated a population‐based consecutive cohort newly diagnosed patients with MM admitted during a defined time period to hospitals in Denmark, Norway, and Sweden. The impact of treatment modality on the prognostic importance of specific chromosomal aberration was investigated, with special reference to gain 1q21. The median follow‐up of patients still alive at analysis was 40 months for the high‐dose (HDT)‐treated ones and 29 months for the whole population. Three hundred forty‐seven patients with a known 1q21 status were included in this study. The 347 patients were divided into three groups, that is, 119 patients with the 1q21 gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p), t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups were compared in terms of overall survival (OS), time to progression (TTP), and response. The 3‐yr OS for patients with gain 1q21 was 60% compared to patients with OA 74% and NO 82% (gain 1q21 vs. NO < 0.001; gain 1q21 vs. OA P = 0.095). If treated with PI or IMiDs, the 3‐yr OS was 58% for patients with gain 1q21 compared to patients with OA 78% and NO 78%, respectively (P = 0.041, = 0.140). In HDT patients, the 3‐yr OS was 69% for patients with gain 1q21 compared to patients with OA 84% and NO 88%, respectively (< 0.008, = 0.600). Thus, neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA, approaching the survival in NO. Further, gain 1q21 appears to be one of the most important poor prognostic chromosomal aberrations in multiple myeloma with current treatments. Trials using new drugs or allogeneic transplantation are warranted.
Keywords:multiple myeloma  clinical  chromosomal abberation  gain 1q21
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