PF620 COMPARISON OF RISS AND IMWG RISK STRATIFICATION GUIDELINES WITH GENE EXPRESSION PROFILE SKY92 IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS; RESULTS FROM THE PROMMIS TRIAL
Authors: P. Hari, S. Lentzsch, D. Siegel, S.Z. Usmani, B. Dhakal, A. Rossi, C. Rosenbaum, S. Leng, D. Bhutani, M. Bhutani, N. Biran, D. Vesole, L. Stork‐Sloots, F. de Snoo, B. Dumee, M.H. van Vliet, R. Niesvizky
Journal: HemaSphere (2019)

Background: Multiple Myeloma (MM) is recognized as a heterogeneous group of patients with varying response and outcome of their disease, associated with various risk factors including genetic abnormalities. Genetic abnormalities are important factors for risk stratification guidelines such as outlined in the IMWG consensus. High risk gene expression profiling results are included in these guidelines for stratifying patients as high risk. One such gene expression profile is the SKY92; it is a 92‐gene prognostic signature which classifies MM patients into a “high” or “standard” risk group. It has been reported to be a robust predictor for Overall Survival (OS) as well as Progression Free Survival (PFS) (Kuiper 2012, Kuiper 2015). The PRospective Observational Multiple Myeloma Impact Study (PROMMIS) trial (NCT02911571) assess the impact of SKY92 on treatment intention. Aims: The aim of this current sub‐study is to compare SKY92 risk results with rISS and the IMWG consensus on risk stratification in PROMMIS patients and to determine the potential impact of gene expression profile determined risk implementation in clinical practice. Methods: Patients with MM according to the IMWG criteria and an ECOG performance status ≤ 3 had their BM aspirate analyzed using the MMprofiler with SKY92. Physicians completed questionnaires capturing treatment intention and MM risk prior to and post receiving the SKY92 result. Genetic abnormalities were determined in local laboratories. Genetic abnormalities defined as high risk in the IMWG consensus: t(4;14), del17p, and gain1q. The IMWG consensus (Chng 2014) and rISS classification (Palumbo 2015) were compared with SKY92 risk classification. Results: Thirty‐eight patients have been enrolled in the PROMMIS trial so far. Prior to SKY92 physicians classified 22 patients (58%) as high risk. SKY92 classified 14 patients (37%) as high risk. The majority of patients (n = 27; 71%) were r‐ISS stage II, of whom 10 were SKY92 high risk. Eight patients were r‐ISS I, of whom 2 were SKY92 high risk. Only one patient was r‐ISS stage III; who was also classified as high risk by SKY92. Eighteen patients carried one or more high risk abnormalities as defined in the IMWG consensus: t(4;14) (n = 1), del17p (n = 5), and gain1q (n = 13). SKY92 classified 8 of these patients as high risk and the other 10 as standard risk. Twenty patients had no IMWG consensus high risk genetic abnormality detected and SKY92 classified 6 of these patients as high risk. Physician risk classification and treatment intention changed in 16 out of 38 (42%) patients after receiving SKY92. For 24 patients (63%) the physician indicated the SKY92 result to be helpful. Furthermore, the treatment intention for 34 (89%) of patients was in line with the SKY92 result. Summary/Conclusion: Risk stratification by rISS and IMWG consensus missed a substantial number of high risk MM patients that could be identified using SKY92. Overall, physician risk classification changed for 42% of patients after receiving the SKY92 result. The final treatment intention by the physician after knowing all factors including SKY92 was in agreement with SKY92 for 34 out of 38 patients This underlines the relevance and need for assessment of SKY92 in MM patients, and associated risk stratified treatment paradigm.