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Peer-reviewedCC BYHematology, Transfusion and Cell Therapy

SERUM IL-12 PREDICTS MINIMAL RESIDUAL DISEASE NEGATIVITY AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA

  • Alexandra Fernandes CALLERA1
  • Evandro Secchi ROSA1
  • Fernando CALLERA2
  1. 1Centro de Hematologia do Vale, São José dos Campos, SP, Brazil
  2. 2Faculdade de Ciências Médicas de São José dos Campos (HUMANITAS), São José dos Campos, SP, Brazil; Centro de Hematologia do Vale, São José dos Campos, SP, Brazil
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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.

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Cite

BibTeXRIS
BibTeX
@article{callera2026serum,
  title = {{SERUM IL-12 PREDICTS MINIMAL RESIDUAL DISEASE NEGATIVITY AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA}},
  author = {Alexandra Fernandes CALLERA and Evandro Secchi ROSA and Fernando CALLERA},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107934},
  url = {https://doi.org/10.1016/j.htct.2026.107934},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - SERUM IL-12 PREDICTS MINIMAL RESIDUAL DISEASE NEGATIVITY AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA
AU  - Alexandra Fernandes CALLERA
AU  - Evandro Secchi ROSA
AU  - Fernando CALLERA
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107934
UR  - https://doi.org/10.1016/j.htct.2026.107934
AB  - 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.
SN  - 2531-1379
SN  - 2531-1387
ER  -