Background: Hodgkin Lymphoma is characterized by an inflammatory background in which the reactive myeloid cells may exert an immune suppressive effect that advances progression of disease. Immunoglobulin M is first antibody isotype to be produced during an immune response, but it plays also an immunoregulatory role, therefore we investigated if it could have any clinical impact on prognosis.
Experimental design: In this retrospective, observational, single – center study, we evaluated 212 newly diagnosed Hodgkin Lymphoma (HL) patients, including 132 advanced stage cases, with a median follow up of 60.3 months (range 60 - 204); 109 (51%) were men, with a median age of 31 years (range 15-77), 64 patients showed bulky disease, while 119 suffered from B symptoms at the onset. The median baseline values for IgM, IgA and IgG were, respectively: 86.0 (range 5.0-336.0 mg/dL), 197.5 (range 5.0- 336.0 mg/dL) and 1110.00 (range 157.0-2763.0 mg/dL). 49/212 (23%) patients had a baseline IgM value lower than 50mg/dL. White blood cell count and type were determined by electrical impedance method. Nephelometry was used for immunoglobulins quantification.
Results: PFS at 60 months was 54.1% versus 81.1 % respectively in patients with IgM ≤50 mg/dL or IgM>50 mg/dL (p<0.001). A level of 50 mg/dl of IgM at baseline resulted in 84.1% sensitivity and 45.5% specificity in predicting achievement of complete response in the whole cohort (area under curve - AUC - 0.62, p=0.013). In multivariate analysis, only baseline IgM ≤50 mg/dl and presence of large nodal mass (< 7 cm) were independent baseline variables able to predict clinical outcome while after two cycles of treatment only IgM ≤50 mg/dl at baseline and PET-2 status were independent predictors of PFS. Thus, we stratified the advanced stage patients in three groups based on clinical variables available at diagnosis: low risk group was defined as absence of LNM and baseline IgM >50; standard-risk was defined by either presence of LNM or baseline IgM ≤50 mg/dL; high risk group was defined by both presence of LNM and IgM ≤50 mg/dL at baseline. The 60-months PFS estimates were significantly different among the three groups, respectively 83.5, 59.5 and 40.0%, p=<0.0001.
Conclusion: IgM amount at diagnosis is a valuable prognostic factor much earlier than PET-2 and it can also provide information in PET-2 negative patients. This can help identify at baseline different HL classes at risk of treatment failure.