Multiple myeloma (MM) is a malignancy with varying survival outcomes and drivers of disease progression. Existing MM staging tools were developed using data from newly diagnosed patients. As patient characteristics and disease-related factors change between diagnosis and the initiation of second-line (2L) treatment, an unmet need exists for a tool that can evaluate risk of death at first relapse. We have developed a risk stratification algorithm (RSA) using data from patients with MM who were at 2L. Hazard ratios for independent predictors of overall survival (OS) were derived from a Cox models, and individual patient scores were calculated for total risk. K-adaptive partitioning for survival was used to stratify patients into groups based on their scores. Relative risk doubled with ascending risk group; median OSs for patients in group 1 (lowest risk)-4 (highest risk) were 61·6, 29·6, 14·2 and 5·9 months, respectively. Differences in OS between risk groups were significant. Similar stratification was observed when the RSA was applied to an external validation data set. In conclusion, we have developed a validated RSA that can quantify total risk, frailty risk and disease aggressiveness risk, and stratify patients with MM at 2L into groups with profoundly different survival expectations.

1st Medical Department Clinical Department of Haematology 1st Faculty of Medicine and General Teaching Hospital Charles University Prague Hradec Králové Czech Republic

4th Department of Medicine Haematology Charles University Hospital and Faculty of Medicine Hradec Králové Hradec Králové Czech Republic

Amgen Europe GmbH Rotkreuz Switzerland

Amgen Ltd Uxbridge UK

Department of Haemato oncology University Hospital Ostrava Ostrava Czech Republic

Department of Haematology University Hospital Leuven Leuven Belgium

Department of Internal Medicine 5 University Hospital Heidelberg Heidelberg Germany

Department of Internal Medicine Haematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Pharmerit International Rotterdam the Netherlands

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Novel risk stratification algorithm for estimating the risk of death in patients with relapsed multiple myeloma: external validation in a retrospective chart review

Methodology of a Novel Risk Stratification Algorithm for Patients with Multiple Myeloma in the Relapsed Setting