Survival Improvement in the Last 45 Years in Patients with Multiple Myeloma: Real-World Data from a Single Center
Authors: Rodríguez-Lobato Luis Gerardo , Fernández De Larrea Carlos , Tovar Natalia , Cibeira Maria Teresa , Bladé Joan , Rosinol Laura 
Published: October 2019

Abstract
INTRODUCTION: Multiple myeloma (MM) is the second most common blood cancer, with estimated 5-year overall survival (OS) rate of 50%. Survival rates have steadily increased over last decades due to the introduction of high-dose melphalan with autologous stem cell transplantation (ASCT) and newer drugs (thalidomide, lenalidomide and bortezomib). Nevertheless, most studies in MM do not reflect the true real-world population.
The aims of the present study were to analyze the survival outcomes, as well as to determine the incidence and causes of early mortality and time to next therapy (TTNT) over time, in patients diagnosed with MM, treated and followed at a single institution.
METHODS: We reviewed the clinical records of patients with MM diagnosed at a single institution from January 1970 to December 2015. One thousand one hundred sixty-one patients (591 [50.9%] male; median age at diagnosis 64 years) was the final study population. Median follow-up for alive patients was 5.4 years (range, 0.5-34.4 years). The diagnosis of MM was based on international criteria established during the different periods analyzed. Baseline demographics, clinical and laboratory data, treatment and follow-up were collected. The population was divided into three periods, which included: group A (1970 to 1985), group B (1986 to 1999) and group C (2000 to 2015) (Table 1). The Ethics Committee of the Hospital Clínic of Barcelona approved the study.
RESULTS: The median OS (mOS) of all patients was 3.6 years (95% CI: 3.2-3.8). We observed an improvement in mOS during follow-up (Group A: 1.7 years [95% CI: 1.23-2.06]; Group B: 2.92 years [95% CI: 2.44-3.32]; Group C: 5.01 years [95% CI: 4.31-5.52]; p<0.00001). The 5-year OS were 21%, 32% and 50%, respectively (Figure 1A). These findings were maintained in the stratified analysis according to 3 periods by age: < 65 years old (Group A: 1.9 years [95% CI: 1.19-2.54]; Group B: 3.6 years [95% CI: 3.14-4.92]; Group C: 7.5 years [95% CI: 5.64-9.79]; p<0.00001); 65-75 years old (Group A: 1.5 years [95% CI: 0.86-2.26]; Group B: 2.3 years [95% CI: 1.91-2.96]; Group C: 4.3 years [95% CI 3.8-5.25]; p<0.00001); and >75 years old (Group A: 1.1 years [95% CI: 0.12-2.13]; Group B: 1.8 years [95% CI: 1.30-2.74]; Group C: 2.8 years [95% CI: 1.99-3.24]; p<0.001) (Figure 1B to 1D). In the multivariate Cox proportional hazard model, these periods of time retained its independent prognostic value in terms of OS (Group B: HR=0.66; 95% CI 0.55-0.79; p<0.0001; Group C: HR=0.39; 95% CI 0.32-0.47; p<0.00001; compared with Group A).
The early mortality rate (first 60 days after diagnosis) was 5.7%; 17.1% in the Group A, 5.7% in Group B, and 2.7% in Group C; p<0.001. The most frequent causes of early mortality were disease-related (46.7%, 63.6% and 66.6%; respectively), and infectious complications (36.7%, 22.7%, and 20.0%; respectively).
In terms of time elapse between the start of front-line treatment until the beginning of the subsequent line, the median time to second line treatment in the group A, B and C, were 10.5 months (95% CI: 8.8-14.2), 18.6 months (95% CI: 15.9-21.8), and 26.6 months (95% CI: 23.5-30.7), respectively (p<0.00001) (Figure 1E). In the stratified analysis by age, these positive findings were only observed in the subgroup of patients diagnosed in the period from 2000 to 2015 (<65 years old: 24.6 months [95% CI: 22.1-28.8]; 65-75 years old: 19.1 months [95% CI: 15.6-23.7]; >75 years old: 15 months [95% CI: 9.4-18.5]; p<0.001) (Figure 1F). Regarding subsequent treatment lines (3rd and 4th), we did not observe statistically significant differences in TTNT neither by age nor by treatment periods.
CONCLUSIONS: This study shows that the survival outcome have significantly improved over the last decades in all age groups, including the elderly, due to ASCT and novel drugs. The incidence of early mortality is low, being the most frequent MM progression and infectious complications. Finally, the time to second line treatment has increased, specifically during the period from 2000 to 2015, with no differences in subsequent lines.

Disclosures
Bladé: Janssen: Honoraria. Rosinol:Janssen, Celgene, Amgen, Takeda: Honoraria.