Neuropsychiatric Adverse Events with Monoclonal Antibodies Approved for Multiple Myeloma: An Analysis from the FDA Adverse Event Reporting System

Abstract

Background/Objectives: Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety are limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. Methods: Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsychiatric AE and one of the MM-approved mAbs as the suspected drug (i.e., daratumumab, elotuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. Results: Unknown signals of disproportionate reporting (SDR) included the following: cerebral infarction for daratumumab (n = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC₀₂₅-IC₀₇₅ = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); an altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guillain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthostatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elotuzumab (4; 28.31, 10.58-75.73; 5, 3.24-6.08). Conclusions: Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsychiatric AEs, including GBS, further investigations are necessary.

Keywords: FAERS; monoclonal antibody; multiple myeloma; neuropsychiatric adverse events; pharmacovigilance.

Figure 1

Database cleaning and cases selection flowchart. AE = adverse event; ICSR = individual case safety report; MM = multiple myeloma; and PT = Preferred Term.

Figure 2

Time to onset of neuropsychiatric AEs. The data are sorted in descending order of frequency and presented as a box plot, with the box extending from the first quartile (Q1) to the third quartile (Q3) and a horizontal line in the middle representing the median time to onset (TTO).