P-183: Monoclonal Gammopathy of Uncertain Significance (MGUS) like Profile in Transplant-eligible Multiple Myeloma (MM) Patients: Clinic-Biological Characteristics and Prognosis Significance

Introduction: The MGUS-like model allows to identify three groups of MM patients with different progression-free survival (PFS) by quantification of plasma cells (PCs) and clonal PCs in bone marrow (BM): MGUS-like, intermediate, and MM-like groups. However, the characteristics of these groups and their effect on response were not evaluated, furthermore, the model has not been validated in real-world patients.

Methods: A retrospective observational study was conducted including patients who received autologous stem cell transplantation (ASCT) between 2005-2023. The MGUS-like profile was determined at diagnosis using the calculator available in https://www.mgus-like.com/.

Results: The model was applied in 402 patients: 38 were MGUS-like (10%), 182 were intermediate and 182 were MM-like profiles (both 45%). MGUS-like patients had less anemia (Hb ≤10 g/dL: 7%), renal failure (CrCl ≥2 mg/dL, 0%), BM infiltration assessed by cytology (≤10% of PCs: 71%), and less secretory disease, but more presence of lytic lesions (87%) and paraskeletal plasmacytomas (70%), compared to the intermediate and MM-like profiles (all P < 0.05). No MGUS-like patients were ISS/R-ISS 3, whereas these patients enriched the intermediate (23%/13%) and MM-like groups (36%/20%) (P < 0.05). MGUS-like patients had fewer high-risk cytogenetic abnormalities than intermediate and MM-like patients: t(4;14) (4% vs 8% vs 11%), t(14;16) (0% vs 2% vs 2%) and gan1q (0% vs 25% vs 31%) (all P < 0.05). No differences were observed in del1p. However, del17p was more frequent in the MGUS-like than the intermediate (9%) and MM-like groups (22% vs 9 vs 6%; P < 0.05).

The median age at ASCT was 60 years, and 90% of patients received ASCT in 1^st line. No differences were observed among groups in induction, consolidation, and maintenance schemes. More patients with MGUS-like profile achieved complete response with minimal residual disease (MRD) negative (75%) compared to the intermediate (57%) and the MM-like profiles (53%) (both P < 0.05).

With a median of follow-up of 56 months, the median PFS of MGUS-like group was not reached and was significantly prolonged compared to the remaining groups: intermediate (63 months) and MM-like (42 months) (both P < 0.05). Notably, no differences were observed in PFS of MGUS-like patients according to del17p status (both not reached). Also, in those patients with ≥8 years of follow-up, MGUS-like patients had excellent outcome, with an 8-year PFS of 80%, compared with 53% in the intermediate (P=0.06) and 41% in the MM-like groups (P < 0.05).

Conclusions: The MGUS-like profile identified transplant-eligible patients with less aggressive disease and with fewer high-risk abnormalities but with more lytic lesions and plasmacytomas. The MGUS-like profile was a predictor factor for MRD negativity. The prognostic model was validated in our series and the MGUS-like group presented longer PFS and could be a prognostic tool to predict the long-term efficacy of ASCT.