Aspirin Use and Survival in Multiple Myeloma Patients
Authors: Marinac Catherine R. , Colditz Graham A , Rosner Bernard , Ghobrial Irene M. , Birmann Brenda M 
Published: October 2019

Abstract
Background: Multiple myeloma (MM) is a lethal malignancy with 5- and 10-year survival rates of 46.7% and 20.6%, respectively. Marked advancements in treatment have improved survival within the last decade but are expensive and do not achieve cure. It is known that inflammation is important in MM pathogenesis, and regular aspirin use has been shown to confer a reduced risk of incident MM. However, the influence of aspirin on survival after diagnosis of MM is unknown. We investigated this question prospectively in two large cohorts.
Methods: We identified 567 men and women diagnosed with MM between 1980 and 2012 in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). Participants in both cohorts reported aspirin intake biennially on follow-up questionnaires beginning in 1986 in HPFS and 1980 in NHS. Using multivariable Cox proportional hazards regression models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for MM-specific and overall mortality through 2015 according to aspirin use patterns. We also examined differences in MM clinical characteristics by aspirin use patterns in a subset of participants with available clinical data.
Results: After a median follow-up of 40 months, there were 135 total deaths (76%) and 107 MM−specific deaths (60%) among 177 participants who used aspirin after MM diagnosis, compared with 222 total deaths (90%) and 195 MM−specific deaths (79%) among 247 participants who did not use aspirin. Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for MM−specific mortality of 0.55 (95% confidence interval [CI], 0.41, 0.73) and for overall mortality of 0.58 (95% CI, 0.45, 0.75), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, pre-diagnosis aspirin use, and number of comorbidities. We also observed evidence of a dose response association between postdiagnosis aspirin quantity for both MM-specific and overall mortality (P-trend <0.01). The association between postdiagnosis aspirin use and MM-specific and overall mortality were not materially different in models that excluded deaths that occurred within 12 months of completing the postdiagnosis aspirin assessment. We could not adjust for first line therapy, but adjustment for year of diagnosis may partially control for first line therapy in these cohorts. In a subsample (n=225) of participants with clinical data available, we did not observe statistically significant differences in the clinically presenting features of MM by post diagnosis aspirin use. We also did not observe statistically significant associations between pre-diagnosis quantity or duration of aspirin use and MM-specific or overall mortality.
Conclusions: Although lack of adjustment for clinical parameters is a limitation, the findings suggest that aspirin use after MM diagnosis is associated with a lower risk of MM−specific and overall mortality.

Disclosures
Ghobrial: Celgene: Consultancy; BMS: Consultancy; Janssen: Consultancy; Takeda: Consultancy.