Serum Il-12 Predicts Minimal Residual Disease Negativity After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Myeloma
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Minimal residual disease (MRD) is one of the strongest prognostic markers in multiple myeloma (MM). However, accessible biomarkers capable of predicting MRD status after autologous hematopoietic stem cell transplantation (ASCT) remain limited. Interleukin-12 (IL-12) plays a central role in antitumor immune responses and may reflect immune competence after treatment. Aim To investigate the association between serum IL-12 levels and MRD status after ASCT in patients with MM treated in the Brazilian public healthcare system. Methods Forty-five consecutive patients with MM treated with VCD or VTD induction followed by ASCT were evaluated. Serum IL-12 was measured after hematologic recovery, and MRD was assessed by multiparameter flow cytometry on day +100 after transplantation. Associations between IL-12 and MRD were analyzed using Mann-Whitney and Spearman tests. ROC analysis determined the optimal IL-12 cutoff for predicting MRD negativity. Independent predictors were evaluated using Firth penalized multivariable logistic regression with bootstrap internal validation. Results Patients achieving MRD negativity presented significantly higher serum IL-12 concentrations (p = 0.0002). Among patients with detectable MRD, IL-12 levels showed a strong inverse correlation with clonal plasma cell burden (Spearman ρ = -0.867; p < 0.000001). ROC analysis demonstrated good discriminatory performance (AUC = 0.837), with an optimal cutoff of 189.7 pg/mL (76.9% sensitivity and 84.4% specificity). Patients with IL-12 ≥ 189.7 pg/mL were approximately seven times more likely to achieve MRD negativity than those with lower concentrations (66.7% vs. 10.0%). In multivariable Firth regression, serum IL-12 remained independently associated with MRD negativity (adjusted OR=1.80 per 50 pg/mL increase; 95% CI 1.13–2.87; p = 0.014), together with pre-transplant CR/VGPR (adjusted OR = 6.74; p = 0.027). Internal bootstrap validation demonstrated robust model performance (optimism-corrected AUC = 0.843). Conclusion Serum IL-12 is independently associated with MRD negativity after ASCT and demonstrates good discriminative performance for identifying patients achieving deep response. These findings suggest that IL-12 may represent a simple and clinically applicable biomarker of immune recovery and treatment response in multiple myeloma, warranting prospective validation in larger cohorts.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223106884