OBJECTIVES:  Multiple myeloma is a progressive disease with remission and relapse episodes requiring successive lines of treatment. This study aimed to estimate the latest 5-year overall survival by line of treatment from French population-based registries. METHODS:  Incident cases of multiple myeloma diagnosed in 2008–2009 in 3 French population-based haematological malignancies registries (Côte d’Or, Gironde, and Calvados) were included. Retrospective data collection was conducted to describe patients’ characteristics (International Staging System score, haematopoietic stem cell transplantation [HSCT] status, cytogenetic prognostic factor, biological parameters), treatment usage and disease evolution per treatment line until December 2014. Estimation of progression-free and overall survival by treatment line was conducted using Kaplan-Meier curves and prognostic factors were identified using the flexible parametric hazards model from Royston (Stat Med 2002;21:2175-97). RESULTS:  A total of 345 patients were included (278 (81%) received ≥1 treatment line, 148 (43%) ≥2 treatment lines, 93 (27%) ≥3 treatment lines, 49 (14%) ≥4 treatment lines). Median age was 70 years at treatment initiation with 61% of second line patients previously treated with bortezomib and 41% of third line patients previously treated with lenalidomide. 33% of second line patients previously received HSCT. Five-year overall survival decreased from 43% in first line to 33% in second line, 22% in third line and 21% in fourth line. A similar trend was observed for 2-year progression-free survival with a decrease from 49% in first line to 42% in second line, 25% in third line and 21% in fourth line. Age, past and current treatment and prior HSCT were the main drivers for overall survival. CONCLUSIONS:  This study confirms the decrease in survival with each successive line of treatment. With the availability of new treatment options and combinations, it is anticipated that survival will improve substantially in the coming years.