LAUSR

Simple Summary Multiple myeloma (MM) is a hematologic cancer originating from underlying precursor disorders, called Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). In order to predict the risk of progression from MGUS/SMM to MM, well-known prognostic factors are currently used in the clinical management, but the contribute of myeloma-specific T-cell immunity still remains to be addressed in this context. In this work, we shed light on the relevant dynamics of MM-specific T cells in a long-term cohort of MGUS/SMM patients, in particular describing a new prognostic tool, namely Multi-antigenic Myeloma-specific (MaMs) T-cell assay, which may be useful to assess the presence of a protective MM-specific immunity, possibly representing a novel immunologic marker of effective disease control. Our work can be considered a promising proof-of-concept for future larger studies, aiming to further explore the prognostic impact of MaMs-based tests in the management of patients with monoclonal gammopathies. Abstract Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients’ HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies.