Gene-expression-profiling plus integrated multidisciplinary approach to detect new-generation risk-adapted prognostic index in smoldering myeloma and multiple myeloma (GIMPI).

7558 Background: In our Institution, a prospective study to test the combination of gene-expression-profiling (SKY92 gene signature) and new generation imaging (PET/CT + Whole body MRI) was applied to all consecutive patients affected by smoldering (SMM), newly diagnosed (NDMM) and relapsed/refractory (RRMM) MM and evaluated its potential to predict or correlate with established HR markers of this disease and potentially defining new basis for a personalized treatment. Methods: Patients’ bone marrow aspirate, plasma, imaging and clinical data were collected in our Institute under approved protocol and according to the Declaration of Helsinki guidelines. Results: In this study a cohort of 139 patients referring to our Institute was enrolled (SMM n=47, NDMM n=54 and RRMM n=38): here we present only the molecular part of the study, combination with imaging analysis is currently ongoing. Proportion of patients with SKY92 HR increased from SMM (8.4%) to NDMM (36.7%) and RRMM (53.3%, p=0.0162). Virtual FISH in NDMM patients showed 100% accuracy (95% CI) (100.0-100.0) for both t(4;14) and gain(1q) and of 90.0 (71.4-100.0) for del(17p), and this could be really useful for the daily clinical practice. The concentration of sBCMA was measured in our patients' cohort and in healthy subjects (n=12, control) with a statistically significant increase of sBCMA in the blood of NDMM and RRMM with respect to SMM (p=0.0009, p=0.0222) and control (p<0.0001, p=0.0010). Consistently with the literature, no statistically significant differences were observed among NDMM and RRMM. Thus, we hypothesize that SKY92 HR could capture patients with high levels of sBCMA. We compared the concentration of this disease biomarker among SR and HR including SMM, NDMM and RRMM patients and we observed increased levels of sBCMA in HR patients with respect to SR (p=0.0049). A risk-based intragroup comparison showed a similar trend in SMM and RRMM and, importantly, this result was confirmed in NDMM patients (p=0.0445). However, in this category of MM patients ISS could partially recapitulate differences in sBCMA among risk classes with the only statistically significant difference between Class I and III (p=0.0381). Therefore, we combined ISS with SKY92 and we observed that n=11 patients considered as LR by ISS (Class I), were relocated to the IR from this analysis with an overall improvement in the distribution of sBCMA levels according to risk categories (SR vs HR p=0.0011, IR vs HR p=0.0036). Conclusion: The results of this first pilot Italian study, that in the next future will be framed in a national network contest, strengthen the prognostic relevance of SKY92 based on its potential to (i) predict HR cytogenetic markers of disease; (ii) capture MM patients with high levels of sBCMA supporting the introduction of this GEP-based tool in the clinical diagnostic practice.