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
4 affiliations
- 1Department of Internal Medicine, St. John’s Episcopal Hospital, New York, NY 11691, USA
- 2Department of Internal Medicine, Landmark Medical Center, Woonsocket, RI 02895, USA
- 3Division of Hematologic Malignancies and Cellular Therapeutics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
- 4Stem Cell Transplantation and Cellular Immunotherapy Program, Department of Hematology/Oncology, UMC TLC2 Foundation Cancer Center, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Abstract
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.
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BibTeX
@article{awadallah2026infectious,
title = {{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}},
author = {Carmel Awadallah and Sohaib Irfan and Al-Ola Abdallah and Muhammad Bilal Abid},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203388},
url = {https://www.mdpi.com/2072-6694/18/20/3388},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Carmel Awadallah
AU - Sohaib Irfan
AU - Al-Ola Abdallah
AU - Muhammad Bilal Abid
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203388
UR - https://www.mdpi.com/2072-6694/18/20/3388
AB - 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.
SN - 2072-6694
ER -