P-124: The history of survival improvement in patients with Multiple Myeloma through real-world data in a 45-year period at a single institution

Abstract

<h3>Background</h3> The prognostic landscape of multiple myeloma (MM) has evolved significantly over the last few decades. After the introduction of high-dose melphalan followed by autologous stem cell transplantation (HDM-ASCT) and, more recently, the first generation of proteasome inhibitors and immunomodulatory drugs have been implemented. There are, however, few data measuring such improvement in real-world patients. This study aimed to investigate trends in survival improvement over 45-years, and the associated clinical factors, in an unselected population of patients with MM in a single tertiary center. <h3>Methods</h3> Between 1970 and 2015, 1161 consecutive MM patients were included in the study. Patients were classified into three calendar periods (1970-84, 1985-99, and 2000-15), according to the treatment which they received; polychemotherapy, HDM-ASCT, and novel drugs, respectively. We analyzed relative (RS) to accurately evaluate MM-related death rates after excluding the mortality expected in the general population. In addition, we chose the Brenner's period method to estimate RS in patients diagnosed after 2000 in order to detect any recent advance towards statistical cure. <h3>Results</h3> After a median follow-up of 3.6 years (IQR: 1.4-6.5), 953 (82.1%) patients had died and 208 (19.9%) were censored alive. Median follow-up for survivors was 7.7 (IQR: 5.3-12.0) years. Median survival steadily improved from 1.7 years in 1970-1984 to 3.0 years in 1985-1999, and to 5.1 years in 2000-2015 (p<0.001). The estimated proportion of patients diagnosed before 2000 who survived more than 20 years was 6% (95% CI: 4.0-8.0). The 5-year RS improved from 27% in 1970-1984 to 38% in 1985-1999, and 56% in 2000-2015, and the 10-year RS improved from 10%, to 21%, to 33%, respectively. Patients younger than 65 years old, and those with ECOG performance status (PS) < 2, and Durie-Salmon stage I/II benefited the most from the improved survival, mainly in the 2000-2015 period. Nevertheless, even patients with ECOG PS ≥ 2 and Durie Salmon stage III improved their RS after 2000 in comparison with the two precedent calendar periods. At the multivariate Poisson regression analysis, increased age, poor ECOG PS, and advanced Durie-Salmon stage were independently associated with smaller improvements in RS. The estimated RS by Brenner's method in the patients diagnosed between 2000 and 2015 did not showed evidence of bending to the horizontal, which discarded statistical cure. <h3>Conclusions</h3> The survival rates of real-world patients with MM have improved over the last 50 years. The largest improvement was seen in younger patients and in those diagnosed after the year 2000, although older patients and those with more advanced disease or poor PS have also benefitted from increased survival. Unfortunately, there is no evidence for statistical cure and 5.1 years as median survival in the last time period still leaves significant room for improvement.