Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials
Authors: Morabito Fortunato , Zamagni Elena , Conticello Concetta , Pavone Vincenzo , Palmieri Salvatore , Bringhen Sara , Galli Monica , Mangiacavalli Silvia , Derudas Daniele , Rossi Elena , Ria Roberto , Catalano Lucio , Tacchetti Paola , Mele Giuseppe , Vincelli Iolanda Donatella , Martino Enrica Antonia , Vigna Ernesto , Bruzzese Antonella , Mendicino Francesco , Botta Cirino , Mele Anna , Pantani Lucia , Rocchi Serena , Garibaldi Bruno , Cascavilla Nicola , Ballanti Stelvio , Tripepi Giovanni , Frigeri Ferdinando , Falcone Antonetta Pia , Cangialosi Clotilde , Reddiconto Giovanni , Farina Giuliana , Barone Marialucia , Rizzello Ilaria , Iaccino Enrico , Mimmi Selena , Curci Paola , Gamberi Barbara , Musto Pellegrino , De Stefano Valerio , Musso Maurizio , Petrucci Maria Teresa , Offidani Massimo , Di Raimondo Francesco , Boccadoro Mario , Cavo Michele , Neri Antonino , Gentile Massimo 
Published: July 2022

The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P &lt; 0.0001), older age (HR = 1.72; P &lt; 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), &gt;3 previous lines of therapies (HR = 1.67; P &lt; 0.0001), older age (HR = 1.64; P &lt; 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRSKRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P &lt; 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P &lt; 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRSKRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P &lt; 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P &lt; 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRSKRd/EloRd and PRSKRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd.