Prognostic significance of IgG-Kappa positivity detected by serum immunofixation during daratumumab therapy in multiple myeloma
- 1Ankara Medicana International Hospital, Dept. of Hematology, Ankara, Türkiye
- 2Ankara Education and Training Hospital, Dept. of Internal Medicine, Ankara, Türkiye
- 3Balıkesir Atatürk City Hospital, Dept. of Hematology, Balıkesir, Türkiye
Abstract
Background: Daratumumab, an immunoglobulin G kappa (IgG-κ) monoclonal antibody, can co-migrate with endogenous M-protein on serum immunofixation (IF), producing IgG-κ bands that may be misinterpreted as residual disease. We therefore evaluated treatment responses and the prognostic impact of daratumumab-associated IgG-κ IF positivity on progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM).
Methods: We retrospectively analyzed 108 patients with MM treated with daratumumab-containing regimens at any line of therapy between January 2014 and January 2024. Serum IF IgG-κ positivity was assessed both at the first response assessment and during continued treatment. Treatment responses were classified according to the International Myeloma Working Group (IMWG) criteria, and PFS and OS were analyzed using the Kaplan–Meier method, the log-rank test, and multivariable Cox proportional hazards regression.
Results: IgG-κ IF positivity was detected in 85 patients (78.7%) at first response, and the overall response rate to daratumumab was 64.8%. Patients positive at first response had longer PFS (14.0 vs. 7.0 months; P = 0.048) and higher very good partial response/complete response rates (65.9% vs. 43.5%; P = 0.058). In non–IgG-κ myeloma, treatment-emergent positivity was associated with a markedly higher deep-response rate (88.5% vs. 44.2%; P < 0.001) and a reduced risk of progression (hazard ratio 0.17; 95% confidence interval 0.03–0.74; P = 0.018). On multivariable analysis, older age independently predicted mortality, whereas persistent IF positivity did not worsen survival.
Conclusions: IgG-κ IF positivity during daratumumab therapy should not be interpreted as residual disease in isolation; a substantial proportion likely reflects therapeutic antibody interference. Recognizing this interference is important to avoid overestimating residual disease and misclassifying treatment response, and confirmatory assays should be used where available.
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BibTeX
@article{cengiz2026prognostic,
title = {{Prognostic significance of IgG-Kappa positivity detected by serum immunofixation during daratumumab therapy in multiple myeloma}},
author = {Esra Cengiz and Ekin Kırcalı and Rıfat Furkan Aydın and Murat Çınarsoy},
journal = {Upsala Journal of Medical Sciences},
year = {2026},
month = nov,
doi = {10.48101/ujms.v131.14932},
url = {https://doi.org/10.48101/ujms.v131.14932},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prognostic significance of IgG-Kappa positivity detected by serum immunofixation during daratumumab therapy in multiple myeloma
AU - Esra Cengiz
AU - Ekin Kırcalı
AU - Rıfat Furkan Aydın
AU - Murat Çınarsoy
PY - 2026
DA - 2026/11/03
JO - Upsala Journal of Medical Sciences
DO - 10.48101/ujms.v131.14932
UR - https://doi.org/10.48101/ujms.v131.14932
AB - Background: Daratumumab, an immunoglobulin G kappa (IgG-κ) monoclonal antibody, can co-migrate with endogenous M-protein on serum immunofixation (IF), producing IgG-κ bands that may be misinterpreted as residual disease. We therefore evaluated treatment responses and the prognostic impact of daratumumab-associated IgG-κ IF positivity on progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Methods: We retrospectively analyzed 108 patients with MM treated with daratumumab-containing regimens at any line of therapy between January 2014 and January 2024. Serum IF IgG-κ positivity was assessed both at the first response assessment and during continued treatment. Treatment responses were classified according to the International Myeloma Working Group (IMWG) criteria, and PFS and OS were analyzed using the Kaplan–Meier method, the log-rank test, and multivariable Cox proportional hazards regression. Results: IgG-κ IF positivity was detected in 85 patients (78.7%) at first response, and the overall response rate to daratumumab was 64.8%. Patients positive at first response had longer PFS (14.0 vs. 7.0 months; P = 0.048) and higher very good partial response/complete response rates (65.9% vs. 43.5%; P = 0.058). In non–IgG-κ myeloma, treatment-emergent positivity was associated with a markedly higher deep-response rate (88.5% vs. 44.2%; P < 0.001) and a reduced risk of progression (hazard ratio 0.17; 95% confidence interval 0.03–0.74; P = 0.018). On multivariable analysis, older age independently predicted mortality, whereas persistent IF positivity did not worsen survival. Conclusions: IgG-κ IF positivity during daratumumab therapy should not be interpreted as residual disease in isolation; a substantial proportion likely reflects therapeutic antibody interference. Recognizing this interference is important to avoid overestimating residual disease and misclassifying treatment response, and confirmatory assays should be used where available.
SN - 0300-9734
SN - 2000-1967
ER -