Adverse Pulmonary Reactions Associated With Proteasome Inhibitors in Multiple Myeloma: A Disproportionality Analysis of the FDA Adverse Event Reporting System
Author(s)
Muhammed F. KT1, Beema T. Yoosuf, PhD2, Dipika Bansal, MD3.
1PhD Research Scholar, National Institute of Pharmaceutical Education and Research, Mohali, India, 2NIPER, Mohali, India, 3National Institute of Pharmaceutical Education and Research, Mohali SAS Nagar, India.
1PhD Research Scholar, National Institute of Pharmaceutical Education and Research, Mohali, India, 2NIPER, Mohali, India, 3National Institute of Pharmaceutical Education and Research, Mohali SAS Nagar, India.
OBJECTIVES: The incidence of adverse pulmonary reactions associated with proteasome inhibitors in multiple myeloma therapy remains poorly characterized. Although these agents are effective, concerns persist regarding their long-term safety due to limited data on rare and delayed adverse events (AEs). To evaluate the incidence of adverse pulmonary reactions in multiple myeloma patients treated with the proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib.
METHODS: The FDA Adverse Event Reporting System (FAERS) was accessed using Open Vigil 2.1 MedDRA v24, covering data up to September 2023. Disproportionality analysis was performed using the proportional reporting ratio (PRR) and reporting odds ratio (ROR). A probable drug-event association was defined per Evans 2001 criteria (n>2, chi2>4, PRR>2, ROR>1). Signal refinement was conducted by restricting drug roles to "primary suspect" status.
RESULTS: In the FAERS database, AEs were reported in association with carfilzomib, ixazomib, and bortezomib, involving 12,513, 18,123, and 43,195 patients, respectively. A detailed analysis identified significant disproportionality signal scores for 68 Preferred Terms (PTs) categorized under the System Organ Classes (SOCs) of “Respiratory, thoracic, and mediastinal disorders” and “Infections and infestations”. Pneumonia was reported in 1,126 cases associated with ixazomib (PRR = 4.87, ROR = 4.82), 457 cases with carfilzomib (PRR = 2.85, ROR = 2.66), and 1,847 cases with bortezomib (PRR = 3.30, ROR = 3.24). For acute pulmonary oedema, 9 cases were linked to ixazomib (PRR = 2.47, ROR = 1.28), 31 cases to carfilzomib (PRR = 12.44, ROR = 8.74), and 40 cases to bortezomib (PRR = 4.57, ROR = 3.35). Most associations remained statistically significant even after signal refinement.
CONCLUSIONS: The study identified significant disproportionality signals associated with proteasome inhibitors and adverse pulmonary events. These findings underscore the importance of considering patient comorbidities and concomitant medications to optimize patient care and mitigate associated risks.
METHODS: The FDA Adverse Event Reporting System (FAERS) was accessed using Open Vigil 2.1 MedDRA v24, covering data up to September 2023. Disproportionality analysis was performed using the proportional reporting ratio (PRR) and reporting odds ratio (ROR). A probable drug-event association was defined per Evans 2001 criteria (n>2, chi2>4, PRR>2, ROR>1). Signal refinement was conducted by restricting drug roles to "primary suspect" status.
RESULTS: In the FAERS database, AEs were reported in association with carfilzomib, ixazomib, and bortezomib, involving 12,513, 18,123, and 43,195 patients, respectively. A detailed analysis identified significant disproportionality signal scores for 68 Preferred Terms (PTs) categorized under the System Organ Classes (SOCs) of “Respiratory, thoracic, and mediastinal disorders” and “Infections and infestations”. Pneumonia was reported in 1,126 cases associated with ixazomib (PRR = 4.87, ROR = 4.82), 457 cases with carfilzomib (PRR = 2.85, ROR = 2.66), and 1,847 cases with bortezomib (PRR = 3.30, ROR = 3.24). For acute pulmonary oedema, 9 cases were linked to ixazomib (PRR = 2.47, ROR = 1.28), 31 cases to carfilzomib (PRR = 12.44, ROR = 8.74), and 40 cases to bortezomib (PRR = 4.57, ROR = 3.35). Most associations remained statistically significant even after signal refinement.
CONCLUSIONS: The study identified significant disproportionality signals associated with proteasome inhibitors and adverse pulmonary events. These findings underscore the importance of considering patient comorbidities and concomitant medications to optimize patient care and mitigate associated risks.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EPH11
Topic
Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Oncology