Infectious Complications and Toxicities of the Teclistamab Plus Daratumumab Combination in Relapsed or Refractory Multiple Myeloma: A Disproportionality and Drug–Interaction Analysis of the FDA Adverse Event Reporting System

Background: Teclistamab plus daratumumab (Tec-Dara) was approved in March 2026 for relapsed or refractory multiple myeloma, but infections are frequent. We hypothesized that dual BCMA- and CD38-directed immune depletion causes infectious toxicity exceeding that expected from either agent alone. Methods: In the FDA Adverse Event Reporting System (FAERS; Q4 2022–Q4 2025; all combination reports pre-approval), we compared reports listing both agents (n = 353) with teclistamab-only (n = 2774) and daratumumab-only (n = 19,230) reports. Interaction was quantified as Ω = RORcombination/(RORteclistamab × RORdaratumumab), where ROR is the reporting odds ratio, with sensitivity analyses addressing calendar period, sparse counts, comparator, and confounding. Results: Pneumonia (Ω, 1.50; 95% CI, 1.06–2.12) and influenza (Ω, 2.63; 95% CI, 1.20–5.77) were reported more often than expected. The pneumonia estimate increased against a myeloma-restricted background and after covariate adjustment, but was no longer statistically significant after excluding reports co-listing immunomodulatory drugs or proteasome inhibitors or with a relapsed-disease daratumumab comparator. Cytokine release syndrome, neurotoxicity, and cytopenias were reported less often than expected, a reporting pattern rather than protection. A bone marrow failure signal rested on few reports and is hypothesis-generating only. Conclusions: Consistent with our hypothesis, Tec-Dara was associated with higher-than-expected reporting of respiratory infections, although confounding by treatment population cannot be excluded. Any new respiratory symptom or fever warrants same-day evaluation.