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Plasma Cell Disorders
Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs
Ferrata Storti Foundation
Haematologica 2020 Volume 105(1):193-200
Vittorio Montefusco,1 Francesca Gay,2 Stefano Spada,2 Lorenzo De Paoli,3 Francesco Di Raimondo,4 Rossella Ribolla,5 Caterina Musolino,6 Francesca Patriarca,7 Pellegrino Musto,8 Piero Galieni,9 Stelvio Ballanti,10 Chiara Nozzoli,11 Nicola Cascavilla,12 Dina Ben-Yehuda,13 Arnon Nagler,14 Roman Hajek,15 Massimo Offidani,16 Anna Marina Liberati,17
Pieter Sonneveld,18 Michele Cavo,19 Paolo Corradini20 and Mario Boccadoro2
1Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; 2Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero- Universitaria Città della Salute e della Scienza di Torino, Torino, Italy; 3Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont and Maggiore Hospital, Novara, Italy; 4Division of Hematology, Ospedale Ferrarotto, Azienda Policlinico-Ospedale Vittorio Emanuele, University of Catania, Catania, Italy; 5Department of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy; 6Division of Haematology, University of Messina, Messina, Italy; 7DAME, Udine University, Udine, Italy; 8Hematology and Stem Cell Transplantation Unit, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy; 9U.O.C. Ematologia e Trapianto di Cellule Staminali Emopoietiche, Ospedale Mazzoni, Ascoli Piceno, Italy; 10Sezione di Ematologia e Immunologia Clinica, Ospedale Santa Maria della Misericordia di Perugia, Perugia, Italy; 11Cellular therapies and Transfusion Medicine Unit, Careggi University Hospital, Firenze, Italy; 12Department of Hematology and Stem Cell Transplant Unit, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy; 13Division of Hematology, Hadassah Ein-Kerem Medical Center, Jerusalem, Israel; 14Hematology Division, Chaim Sheba Medical Center, Tel-HaShomer, Israel; 15Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic and Faculty of Medicine, Ostrava University, Ostrava, Czech Republic; 16Division of Hematology, Ospedali Riuniti, Ancona, Italy; 17A O S Maria di Terni, S C Oncoematologia, Terni, Italy; 18Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands; 19Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, "S. Orsola-Malpighi" Hospital, Bologna, Italy and 20Hemato-Oncology Department, University of Milan, Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
ABSTRACT
Extramedullary disease is relatively frequent in multiple myeloma, but our knowledge on the subject is limited and mainly relies on small case series or single center experiences. Little is known regarding the role of new drugs in this setting. We performed a meta-analysis of eight trials focused on the descrip- tion of extramedullary disease characteristics, clinical outcome, and response to new drugs. A total of 2,332 newly diagnosed myeloma patients have been includ- ed; 267 (11.4%) had extramedullary disease, defined as paraosseous in 243 (10.4%), extramedullary plasmocytoma in 12 (0.5%), and not classified in 12 (0.5%) patients. Median progression-free survival was 25.3 months and 25.2 in extramedullary disease and non-extramedullary disease patients, respectively. In multivariate analysis the presence of extramedullary disease did not impact on progression-free survival (hazard ratio 1.15, P=0.06), while other known prognos- tic factors retained their significance. Patients treated with immunomodulatory drugs, mainly lenalidomide, or proteasome inhibitors had similar progression-free survival and progression-free survival-2 regardless of extramedullary disease pres- ence. Median overall survival was 63.5 months and 79.9 months (P=0.01) in extramedullary and non-extramedullary disease patients, respectively, and in mul- tivariate analysis the presence of extramedullary disease was associated with a reduced overall survival (hazard ratio 1.41, P<0.001), in line with other prognostic factors. With the limits of the use of low sensitivity imaging techniques, that lead to an underestimation of extramedullary disease, we conclude that in patients treated with new drugs the detrimental effect of extramedullary disease at diag- nosis is limited, that lenalidomide is effective as are proteasome inhibitors, and that these patients tend to acquire a more aggressive disease in later stages. (EUDRACT2005-004714-32, NCT01063179. NCT00551928, NCT01091831, NCT01093196, NCT01190787, NCT01346787, NCT01857115).
Correspondence:
VITTORIO MONTEFUSCO
vittorio.montefusco@istitutotumori.mi.it
Received: February 13, 2019. Accepted: June 19, 2019. Pre-published: June 20, 2019.
doi:10.3324/haematol.2019.219139
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/1/193
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