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Montefusco, V.1; Gay, F.2; Spada, S.2; De Paoli, L.3; Di Raimondo, F.4; Ribolla, R.5; Musolino, C.6; Patriarca, F.7; Musto, P.8; Galieni, P.9; Ballanti, S.10; Nozzoli, C.11; Cascavilla, N.12; Ben-Yehuda, D.13; Nagler, A.14; Hajek, R.15; Offidani, M.16; Liberati, A. M.17; Sonneveld, P.18; Cavo, M.19; Corradini, P.1; Boccadoro, M.2

doi: 10.1097/01.HS9.0000560696.15754.80
Poster Session I: Myeloma and other monoclonal gammopathies - Clinical

1Hematology, Fondazione IRCCS Istituto Tumori, Milano

2Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino

3Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont and Maggiore Hospital, Novara

4Hematology, Azienda Policlinico-Vittorio Emanuele, University of Catania, Milano

5Hematology, ASST Spedali Civili di Brescia, Brescia

6Hematology, University of Messina, Messina

7Hematology, DAME, Udine University, Udine

8Hematology and Stem cell Transplantation Unit, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture

9Hematology, Ospedale Mazzoni, Ascoli Pieceno

10Hematology, Ospedale Santa Maria della Misericordia di Perugia, Perugia

11Cellular therapies and transfusion medicine unit, Careggi University Hospital, Firenze

12Hematology and Stem Cell Transplant Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy

13Hematology, Hadassah Ein-Kerem Medical Center, Jerusalem

14Hematology, Chaim Sheba Medical Center, Tel-HaShomer, Israel

15Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic

16Hematology, AOU Ospedali Riuniti di Ancona, Ancona

17S C Oncoematologia, A O S Maria di Terni, Terni, Italy

18Hematology, Erasmus University Medical Center, Rotterdam, Netherlands

19Istituto “L & A Seragnoli”, Ospedale S. Orsola - Malpighi, Bologna, Italy

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Multiple myeloma (MM) can be associated with extramedullary disease (EMD). Although EMD is relatively frequent, even at diagnosis, our knowledge on the subject mainly relies on small case series or single center experiences. Remarkably, little is known regarding the role of new drugs on patients presenting with EMD.

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We performed a meta-analysis focused on the description of EMD characteristics, clinical outcome, and response to new drugs.

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We retrospectively analyzed 8 clinical trials enrolling newly diagnosed MM patients. Three trials enrolled transplant eligible, and 5 trials transplant ineligible patients. Three trials included an immunomodulatory (IMiD) drug in the treatment, lenalidomide in almost all cases, 3 trials a proteasome inhibitor (PI), and 4 trials both. We considered the subgroup of patients with EMD, and compared them with patients without EMD. EMD was categorized into paraosseous plasmocytoma (PO) and extramedullary plasmocytoma (EMP).

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A total of 2332 patients were included in this analysis: 267 (11%) had EMD, while 2065 (89%) had no EMD. Median age of EMD patients was 68 years (range 60-74), and 69 years (range 61-74) in patients without EMD. International staging system was I in 119 (45%) and 682 (33%), II in 89 (33%) and 792 (38%), and III in 38 (14%) and 508 (25%) patients with or without EMD, respectively. Clinical trials were based on IMiD in 166 (62%) and 1279 (62%) patients, on a PI in 66 (25%) and 464 (22%) patients, or both in 35 (13%) and 322 (16%) patients with or without EMD, respectively. Patients with EMD had PO in 243 (91%), and an EMP in 12 (4%) cases, while the information was not available for other 12 (4%) patients only. EMD localizations were single in 195 (73%), and multiple in 60 (22%) patients. Median EMD size was 4.5 cm (IQ range 3 - 7). The median follow-up was 62 months (IQ range 34-75) in EMD, and 65 months (IQ range 40-77) in non-EMD patients. Median PFS was 25.3 months (95% CI 21.7 - 28.7) and 25.2 months (95% CI 24.2 - 27.0) (p = NS) in EMD and non-EMD patients, respectively. In multivariate analysis the presence of EMD did not impact PFS (HR 1.15, 95% CI 0.99-1.33; p = 0.06), while other known prognostic factors retained their significance: high risk vs. standard cytogenetic (HR 1.35; p < 0.001), and ISS III vs. I (HR 1.74; p < 0.001). Type of therapy had not impact on PFS: IMiD-based therapy (HR 1.14) and no IMiDs (HR 1.18) (p = 0.86), PI-based therapy (HR 1.33) and no PI, (HR 1.04) (p = 0.12). Median PFS2 was 42.3 months (95% CI 36.3-51.5) in EMD patients, 46.4 months (95% CI 44.1-48.9) in no-EMD patients (Figure).

Median OS was 63.5 months (95% CI 48.2 - 84.7) and 79.9 months (95% CI 75.8 - 88.3) (p = 0.01) in EMD and non-EMD patients, respectively. In multivariate analysis the presence of EMD was associated with a reduced OS (HR 1.41, 95% CI 1.16-1.71; p < 0.001), in line with other known prognostic factors. Type of therapy did not impact OS: IMiD-based therapy (HR 1.38) and no IMiDs (HR 1.47) (p = 0.78), PI-based therapy (HR 1.43) and no PI, (HR 1.39) (p = 0.87).



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We performed the largest analysis of EMD patients at diagnosis. Although our data are mainly referred to POs, we observed that in these patients treated with new drugs, the detrimental effect of EMD at diagnosis was limited, since the median PFS and PFS-2 were similar in non-EMD and EMD patients, and the median OS was modestly reduced in EMD patients. Moreover, we confirmed that PIs are effective towards EMD, and, for the first time, we provide evidence that also lenalidomide is effective in this setting.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.