Interleukin-12 (IL-12) appears to play an antitumor role through immunomodulatory and antiangiogenic mechanisms in human B-cell neoplasms. In a previous study we demonstrated an increase in serum IL-12 levels after bone marrow recovery in Multiple Myeloma (MM) patients who underwent Autologous hematopoietic Stem Cell Transplantation (ASCT). Based on these findings, we hypothesized a possible influence of IL-12 on the positivity of Minimal Residual Disease (MRD) in MM patients treated with ASCT.

From March 2020 to April 2023, 62 patients with newly diagnosed MM, care provided by the National Health System (SUS) were enrolled. All patients were treated with protocols containing bortezomib, cyclophosphamide and dexamethasone (09 CR, 12 VGPR, 41 PR). Blood samples were taken after the characterization of bone marrow functional recovery. IL-12p70 quantification was performed using an ELISA kit (R&D Systems, MN, EUA). MRD testing was carried out by multiparametric flow cytometry 90-days after hospital discharge. Fisher's exact test was used to evaluate the categorical variables and p-values lower than 0.05 were considered significant.

Among the 62 patients, the median IL-12 concentration was 171 pg/mL, ranging from 28 to 971 pg/mL. Overall, MRD absent (MRD-) was found in 26 and present (MRD+) in 36 patients. A scatter plot showed that patients with higher levels of IL-12 had a lower proportion of MRD+; for this reason, patients were divided into groups with values above (A) and below (B) the median IL-12 concentrations, groups A (high IL-12 concentrations, n = 27) and B (low IL-12 concentrations, n = 35), respectively. In group A, 18 had MRD- against 8 MRD- in group B (Odds Ratio = 6.7, 95% CI 2.2–20.7, p = 0.0007).

Despite limitations such as the number of patients from a single center, the quality of remission before transplantation and the techniques used to detect MRD, we observed that 42% of patients showed MRD- and these results are comparable to previous studies that demonstrated absence of MRD in 42% to 58% of MM patients treated with ASCT. Based on the above arguments, the antitumor effect of IL-12 might explain, at least partly, the high concentration of IL-12 in patients without MRD.

Our data suggest that IL-12 levels obtained in the bone marrow recovery phase seem to be inversely associated with the occurrence of MRD.