Regular Aspirin Use and Mortality in Patients with Multiple Myeloma

Catherine R. Marinac; Dong Hoon Lee; Graham A. Colditz; Timothy R. Rebbeck; Bernard Rosner; Mark Bustoros; Irene M. Ghobrial; Brenda M. Birmann

doi:10.1158/1055-9965.EPI-21-0946

Regular Aspirin Use and Mortality in Patients with Multiple Myeloma

Catherine R. Marinac, Dong Hoon Lee, Graham A. Colditz, Timothy R. Rebbeck, Bernard Rosner, Mark Bustoros, Irene M. Ghobrial, Brenda M. Birmann

Department of Sports Industry Studies

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Inflammation is important in multiple myeloma pathogenesis, and regular aspirin use has been shown to confer a reduced risk of multiple myeloma. The influence of aspirin on survival after multiple myeloma diagnosis is unknown. Methods: We identified 436 men and women diagnosed with multiple myeloma between 1980 and 2016 in the Health Professionals Follow-up Study and the Nurses’ Health Study who reported aspirin intake biennially on follow-up questionnaires. Using multivariable Cox proportional hazards regression models, we estimated HRs and 95% confidence intervals (CI) associated with the effect of aspirin use on multiple myeloma–specific and overall mortality. Results: Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for multiple myeloma–specific mortality of 0.61 (95% CI, 0.46–0.79) and for overall mortality of 0.63 (95% CI, 0.49–0.80), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, prediagnosis aspirin use, and number of comorbidities. For postdiagnosis aspirin quantity, we observed a modest trend of reduction in multiple myeloma–specific and all-cause mortality with increasing number of 325-mg tablets of aspirin per week, although the CIs for 1 to <6 and ≥6 tablets overlapped. Results were not materially different before or after the availability of novel therapies (before vs. after the year 2000). Prediagnosis frequency or duration of aspirin use was not significantly associated with multiple myeloma–specific or overall mortality. Conclusions: These findings support the use of aspirin as a complementary strategy to enhance multiple myeloma survival. Impact: Confirmation in samples that have comprehensive clinical information is encouraged.

Original language	English
Pages (from-to)	479-485
Number of pages	7
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	31
Issue number	2
DOIs	https://doi.org/10.1158/1055-9965.EPI-21-0946
Publication status	Published - 2022 Feb

Bibliographical note

Funding Information:
This study was funded in part by the NCI of the NIH under award numbers K07 CA115687 (to B.M. Birmann), R01 CA127435 (to G.A. Colditz), P01 CA87969 (to B.M. Birmann, B. Rosner), UM1 CA186107 (to B.M. Birmann, B. Rosner), U01 CA167552 (to B.M. Birmann, B. Rosner), R21 CA198239 (to B.M. Birmann), F32 CA220859 (to C.R. Marinac), R03 CA204825 (to D.H. Lee), and K22 CA251648 (to C.R. Marinac). This research was also supported by the American Cancer Society under award number PF-17–231–01-CCE (to C.R. Marinac), Clinical Research Professorship (to G.A. Colditz), as well as institutional funds from the Dana–Farber Cancer Institute, and Stand Up To Cancer under award number SU2C-AACR-DT-28-18 (to I.M. Ghobrial). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of Stand Up To Cancer. Finally, we would like to thank the participants and staff of the HPFS and NHS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data.

Funding Information:
This study was funded in part by the NCI of the NIH under award numbers K07 CA115687 (to B.M. Birmann), R01 CA127435 (to G.A. Colditz), P01 CA87969 (to B.M. Birmann, B. Rosner), UM1 CA186107 (to B.M. Birmann, B. Rosner), U01 CA167552 (to B.M. Birmann, B. Rosner), R21 CA198239 (to B.M. Birmann), F32 CA220859 (to C.R. Marinac), R03 CA204825 (to D.H. Lee), and K22 CA251648 (to C.R. Marinac). This research was also supported by the American Cancer Society

Funding Information:
C.R. Marinac reports grants from NCI, Stand Up to Cancer, and American Cancer Society during the conduct of the study. G.A. Colditz reports grants from NCI during the conduct of the study. B. Rosner reports grants from NIH during the conduct of the study. M. Bustoros reports personal fees from Takeda Pharmaceutical Company, Bristol Myers Squibb, and Janssen Pharmaceuticals outside the submitted work. I.M. Ghobrial reports honoraria from Celgene, Bristol-Myers Squibb, Takeda, Amgen, and Janssen; consulting/advisory role with Bristol-Myers Squibb, Novartis, Amgen, Takeda, Celgene, Cellectar, Sanofi, Janssen, Pfizer, Menarini Silicon Bio-systems Oncopeptides, The Binding Site, GlaxoSmithKline, AbbVie, and Adaptive; and travel and accommodations, and expenses from Bristol-Myers Squibb, Novartis, Celgene, Takeda, and Janssen Oncology. Her spouse, William Savage, MD, PhD, is also the Chief Medical Officer at Disc Medicine and holds equity in the company. B.M. Birmann reports grants from NIH/NCI during the conduct of the study as well as grants from American Institute for Cancer Research, NIH/NIAAA, and NIH/NCI outside the submitted work. No disclosures were reported by the other authors.

Publisher Copyright:
©2021 American Association for Cancer Research

All Science Journal Classification (ASJC) codes

Epidemiology
Oncology

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10.1158/1055-9965.EPI-21-0946

Cite this

@article{24b525a775fe4632946229c5ae9be6af,

title = "Regular Aspirin Use and Mortality in Patients with Multiple Myeloma",

abstract = "Background: Inflammation is important in multiple myeloma pathogenesis, and regular aspirin use has been shown to confer a reduced risk of multiple myeloma. The influence of aspirin on survival after multiple myeloma diagnosis is unknown. Methods: We identified 436 men and women diagnosed with multiple myeloma between 1980 and 2016 in the Health Professionals Follow-up Study and the Nurses{\textquoteright} Health Study who reported aspirin intake biennially on follow-up questionnaires. Using multivariable Cox proportional hazards regression models, we estimated HRs and 95% confidence intervals (CI) associated with the effect of aspirin use on multiple myeloma–specific and overall mortality. Results: Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for multiple myeloma–specific mortality of 0.61 (95% CI, 0.46–0.79) and for overall mortality of 0.63 (95% CI, 0.49–0.80), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, prediagnosis aspirin use, and number of comorbidities. For postdiagnosis aspirin quantity, we observed a modest trend of reduction in multiple myeloma–specific and all-cause mortality with increasing number of 325-mg tablets of aspirin per week, although the CIs for 1 to <6 and ≥6 tablets overlapped. Results were not materially different before or after the availability of novel therapies (before vs. after the year 2000). Prediagnosis frequency or duration of aspirin use was not significantly associated with multiple myeloma–specific or overall mortality. Conclusions: These findings support the use of aspirin as a complementary strategy to enhance multiple myeloma survival. Impact: Confirmation in samples that have comprehensive clinical information is encouraged.",

author = "Marinac, {Catherine R.} and Lee, {Dong Hoon} and Colditz, {Graham A.} and Rebbeck, {Timothy R.} and Bernard Rosner and Mark Bustoros and Ghobrial, {Irene M.} and Birmann, {Brenda M.}",

note = "Funding Information: This study was funded in part by the NCI of the NIH under award numbers K07 CA115687 (to B.M. Birmann), R01 CA127435 (to G.A. Colditz), P01 CA87969 (to B.M. Birmann, B. Rosner), UM1 CA186107 (to B.M. Birmann, B. Rosner), U01 CA167552 (to B.M. Birmann, B. Rosner), R21 CA198239 (to B.M. Birmann), F32 CA220859 (to C.R. Marinac), R03 CA204825 (to D.H. Lee), and K22 CA251648 (to C.R. Marinac). This research was also supported by the American Cancer Society under award number PF-17–231–01-CCE (to C.R. Marinac), Clinical Research Professorship (to G.A. Colditz), as well as institutional funds from the Dana–Farber Cancer Institute, and Stand Up To Cancer under award number SU2C-AACR-DT-28-18 (to I.M. Ghobrial). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of Stand Up To Cancer. Finally, we would like to thank the participants and staff of the HPFS and NHS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. Funding Information: This study was funded in part by the NCI of the NIH under award numbers K07 CA115687 (to B.M. Birmann), R01 CA127435 (to G.A. Colditz), P01 CA87969 (to B.M. Birmann, B. Rosner), UM1 CA186107 (to B.M. Birmann, B. Rosner), U01 CA167552 (to B.M. Birmann, B. Rosner), R21 CA198239 (to B.M. Birmann), F32 CA220859 (to C.R. Marinac), R03 CA204825 (to D.H. Lee), and K22 CA251648 (to C.R. Marinac). This research was also supported by the American Cancer Society Funding Information: C.R. Marinac reports grants from NCI, Stand Up to Cancer, and American Cancer Society during the conduct of the study. G.A. Colditz reports grants from NCI during the conduct of the study. B. Rosner reports grants from NIH during the conduct of the study. M. Bustoros reports personal fees from Takeda Pharmaceutical Company, Bristol Myers Squibb, and Janssen Pharmaceuticals outside the submitted work. I.M. Ghobrial reports honoraria from Celgene, Bristol-Myers Squibb, Takeda, Amgen, and Janssen; consulting/advisory role with Bristol-Myers Squibb, Novartis, Amgen, Takeda, Celgene, Cellectar, Sanofi, Janssen, Pfizer, Menarini Silicon Bio-systems Oncopeptides, The Binding Site, GlaxoSmithKline, AbbVie, and Adaptive; and travel and accommodations, and expenses from Bristol-Myers Squibb, Novartis, Celgene, Takeda, and Janssen Oncology. Her spouse, William Savage, MD, PhD, is also the Chief Medical Officer at Disc Medicine and holds equity in the company. B.M. Birmann reports grants from NIH/NCI during the conduct of the study as well as grants from American Institute for Cancer Research, NIH/NIAAA, and NIH/NCI outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright}2021 American Association for Cancer Research",

year = "2022",

month = feb,

doi = "10.1158/1055-9965.EPI-21-0946",

language = "English",

volume = "31",

pages = "479--485",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "2",

}

TY - JOUR

T1 - Regular Aspirin Use and Mortality in Patients with Multiple Myeloma

AU - Marinac, Catherine R.

AU - Lee, Dong Hoon

AU - Colditz, Graham A.

AU - Rebbeck, Timothy R.

AU - Rosner, Bernard

AU - Bustoros, Mark

AU - Ghobrial, Irene M.

AU - Birmann, Brenda M.

N1 - Funding Information: This study was funded in part by the NCI of the NIH under award numbers K07 CA115687 (to B.M. Birmann), R01 CA127435 (to G.A. Colditz), P01 CA87969 (to B.M. Birmann, B. Rosner), UM1 CA186107 (to B.M. Birmann, B. Rosner), U01 CA167552 (to B.M. Birmann, B. Rosner), R21 CA198239 (to B.M. Birmann), F32 CA220859 (to C.R. Marinac), R03 CA204825 (to D.H. Lee), and K22 CA251648 (to C.R. Marinac). This research was also supported by the American Cancer Society under award number PF-17–231–01-CCE (to C.R. Marinac), Clinical Research Professorship (to G.A. Colditz), as well as institutional funds from the Dana–Farber Cancer Institute, and Stand Up To Cancer under award number SU2C-AACR-DT-28-18 (to I.M. Ghobrial). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of Stand Up To Cancer. Finally, we would like to thank the participants and staff of the HPFS and NHS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. Funding Information: This study was funded in part by the NCI of the NIH under award numbers K07 CA115687 (to B.M. Birmann), R01 CA127435 (to G.A. Colditz), P01 CA87969 (to B.M. Birmann, B. Rosner), UM1 CA186107 (to B.M. Birmann, B. Rosner), U01 CA167552 (to B.M. Birmann, B. Rosner), R21 CA198239 (to B.M. Birmann), F32 CA220859 (to C.R. Marinac), R03 CA204825 (to D.H. Lee), and K22 CA251648 (to C.R. Marinac). This research was also supported by the American Cancer Society Funding Information: C.R. Marinac reports grants from NCI, Stand Up to Cancer, and American Cancer Society during the conduct of the study. G.A. Colditz reports grants from NCI during the conduct of the study. B. Rosner reports grants from NIH during the conduct of the study. M. Bustoros reports personal fees from Takeda Pharmaceutical Company, Bristol Myers Squibb, and Janssen Pharmaceuticals outside the submitted work. I.M. Ghobrial reports honoraria from Celgene, Bristol-Myers Squibb, Takeda, Amgen, and Janssen; consulting/advisory role with Bristol-Myers Squibb, Novartis, Amgen, Takeda, Celgene, Cellectar, Sanofi, Janssen, Pfizer, Menarini Silicon Bio-systems Oncopeptides, The Binding Site, GlaxoSmithKline, AbbVie, and Adaptive; and travel and accommodations, and expenses from Bristol-Myers Squibb, Novartis, Celgene, Takeda, and Janssen Oncology. Her spouse, William Savage, MD, PhD, is also the Chief Medical Officer at Disc Medicine and holds equity in the company. B.M. Birmann reports grants from NIH/NCI during the conduct of the study as well as grants from American Institute for Cancer Research, NIH/NIAAA, and NIH/NCI outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: ©2021 American Association for Cancer Research

PY - 2022/2

Y1 - 2022/2

N2 - Background: Inflammation is important in multiple myeloma pathogenesis, and regular aspirin use has been shown to confer a reduced risk of multiple myeloma. The influence of aspirin on survival after multiple myeloma diagnosis is unknown. Methods: We identified 436 men and women diagnosed with multiple myeloma between 1980 and 2016 in the Health Professionals Follow-up Study and the Nurses’ Health Study who reported aspirin intake biennially on follow-up questionnaires. Using multivariable Cox proportional hazards regression models, we estimated HRs and 95% confidence intervals (CI) associated with the effect of aspirin use on multiple myeloma–specific and overall mortality. Results: Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for multiple myeloma–specific mortality of 0.61 (95% CI, 0.46–0.79) and for overall mortality of 0.63 (95% CI, 0.49–0.80), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, prediagnosis aspirin use, and number of comorbidities. For postdiagnosis aspirin quantity, we observed a modest trend of reduction in multiple myeloma–specific and all-cause mortality with increasing number of 325-mg tablets of aspirin per week, although the CIs for 1 to <6 and ≥6 tablets overlapped. Results were not materially different before or after the availability of novel therapies (before vs. after the year 2000). Prediagnosis frequency or duration of aspirin use was not significantly associated with multiple myeloma–specific or overall mortality. Conclusions: These findings support the use of aspirin as a complementary strategy to enhance multiple myeloma survival. Impact: Confirmation in samples that have comprehensive clinical information is encouraged.

AB - Background: Inflammation is important in multiple myeloma pathogenesis, and regular aspirin use has been shown to confer a reduced risk of multiple myeloma. The influence of aspirin on survival after multiple myeloma diagnosis is unknown. Methods: We identified 436 men and women diagnosed with multiple myeloma between 1980 and 2016 in the Health Professionals Follow-up Study and the Nurses’ Health Study who reported aspirin intake biennially on follow-up questionnaires. Using multivariable Cox proportional hazards regression models, we estimated HRs and 95% confidence intervals (CI) associated with the effect of aspirin use on multiple myeloma–specific and overall mortality. Results: Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for multiple myeloma–specific mortality of 0.61 (95% CI, 0.46–0.79) and for overall mortality of 0.63 (95% CI, 0.49–0.80), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, prediagnosis aspirin use, and number of comorbidities. For postdiagnosis aspirin quantity, we observed a modest trend of reduction in multiple myeloma–specific and all-cause mortality with increasing number of 325-mg tablets of aspirin per week, although the CIs for 1 to <6 and ≥6 tablets overlapped. Results were not materially different before or after the availability of novel therapies (before vs. after the year 2000). Prediagnosis frequency or duration of aspirin use was not significantly associated with multiple myeloma–specific or overall mortality. Conclusions: These findings support the use of aspirin as a complementary strategy to enhance multiple myeloma survival. Impact: Confirmation in samples that have comprehensive clinical information is encouraged.

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U2 - 10.1158/1055-9965.EPI-21-0946

DO - 10.1158/1055-9965.EPI-21-0946

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JF - Cancer Epidemiology Biomarkers and Prevention

IS - 2

ER -

Regular Aspirin Use and Mortality in Patients with Multiple Myeloma

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