PURPOSE: Despite the improvement of therapeutic regimens, several patients with multiple myeloma (MM) still experience early relapse (ER). This subset of patients currently represents an unmet medical need. EXPERIMENTAL DESIGN: We pooled data from seven European multicenter phase II/III clinical trials enrolling 2,190 patients with newly diagnosed MM from 2003 to 2017. Baseline patient evaluation included 14 clinically relevant features. Patients with complete data (n = 1,218) were split into training (n = 844) and validation sets (n = 374). In the training set, a univariate analysis and a multivariate logistic regression model on ER within 18 months (ER18) were made. The most accurate model was selected on the validation set. We also developed a dynamic version of the score by including response to treatment. RESULTS: The Simplified Early Relapse in Multiple Myeloma (S-ERMM) score was modeled on six features weighted by a score: 5 points for high lactate dehydrogenase or t(4;14); 3 for del17p, abnormal albumin, or bone marrow plasma cells >60%; and 2 for λ free light chain. The S-ERMM identified three patient groups with different risks of ER18: Intermediate (Int) versus Low (OR = 2.39, P < 0.001) and High versus Low (OR = 5.59, P < 0.001). S-ERMM High/Int patients had significantly shorter overall survival (High vs. Low: HR = 3.24, P < 0.001; Int vs. Low: HR = 1.86, P < 0.001) and progression-free survival-2 (High vs. Low: HR = 2.89, P < 0.001; Int vs. Low: HR = 1.76, P < 0.001) than S-ERMM Low. The Dynamic S-ERMM (DS-ERMM) modulated the prognostic power of the S-ERMM. CONCLUSIONS: On the basis of simple, widely available baseline features, the S-ERMM and DS-ERMM properly identified patients with different risks of ER and survival outcomes.

Alfred Health Monash University Melbourne Australia

Clinica di Ematologia AOU Ospedali Riuniti di Ancona Ancona Italy

Clinica Ematologica e Unità di Terapie Cellulari Azienda Sanitaria Universitaria Friuli Centrale Università di Udine Udine Italy

Department of Emergency and Organ Transplantation Aldo Moro University School of Medicine Bari Italy

Department of General Surgery and Medical Surgical Specialties Haematology Section University of Catania Catania Italy

Department of Haematooncology University Hospital Ostrava Ostrava Czech Republic

Department of Hematology Erasmus MC Cancer Institute Rotterdam the Netherlands

Division of Hematology Azienda Ospedaliera Papardo Messina Italy

Division of Hematology Department of Translational Medicine University of Eastern Piedmont Novara Italy

Divisione di Ematologia Fondazione IRCCS Istituto Nazionale dei Tumori di Milano; Università degli Studi di Milano Milano Italy

Ematologia Ospedale Casa Sollievo della Sofferenza IRCCS San Giovanni Rotondo Italy

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Hematology and Cell Therapy Unit IRCCS Istituto Tumori 'Giovanni Paolo 2 ' Bari Italy

Hematology Department of Translational and Precision Medicine Azienda Ospedaliera Policlinico Umberto 1 Sapienza University of Rome Rome Italy

Hematology Division ASST Spedali Civili Brescia Brescia Italy

Hematology Division Chaim Sheba Medical Center Tel Hashomer Israel

Hematology St Eugenio Hospital ASL Roma 2 Tor Vergata University Rome Italy

Myeloma Unit Division of Hematology University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Torino Italy

SC Hematology AO Città della Salute e della Scienza Turin Italy

Unit of Hematology and Stem Cell Transplantation AOUC Policlinico Bari Italy

Università degli Studi di Perugia Azienda Ospedaliera Santa Maria Terni Italy

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