PF602 OUTCOME OF EXTRA-MEDULLARY DISEASE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS TREATED WITH NEW DRUGS
Authors: V. Montefusco, F. Gay, S. Spada, L. De Paoli, F. Di Raimondo, R. Ribolla, C. Musolino, F. Patriarca, P. Musto, P. Galieni, S. Ballanti, C. Nozzoli, N. Cascavilla, D. Ben-Yehuda, A. Nagler, R. Hajek, M. Offidani, A.M. Liberati, P. Sonneveld, M. Cavo, P. Corradini, M. Boccadoro
Journal: HemaSphere (2019)

Background: 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. Aims: We performed a meta-analysis focused on the description of EMD characteristics, clinical outcome, and response to new drugs. Methods: 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). Results: 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).Summary/Conclusion: 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.