P1023: COHORT ANALYSIS OF MPN PATIENTS WITH CONCOMITANT MGUS DIAGNOSIS: A RETROSPECTIVE STUDY

Abstract

Background: Patients with a Ph-negative myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), may harbor or develop plasma-cell dyscrasia such as monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), however, the clinical and molecular determinants of this co-occurrence are still uncertain. Aims: The main aim of this study was to evaluate correlation between MGUS and MPN related features and clinical course. Methods: We retrospectively analyzed clinical data from 448 patients with a diagnosis of MPNs according to 2016 WHO criteria, performed from 1989 to 2020 at our Institution. Here, we described the clinical and genetic features of MPN patients with concomitant MGUS. Data collection included NGS panel, cytogenetic analysis, clinical history (including thrombotic events) and pharmacological therapy during the entire MPNs follow up. Results: Among the 448 consecutive patients analyzed, 33 (7.4%) displayed both MPN and MGUS. Twenty-three of them were females while 10 males. MPN diagnosis were ET (12/33, 36%), MF (11/33, 33%), PV (8/33, 24%), or pre-MF (2/33, 6%) at a median age of 61 years (28-84); 25 patients showed JAK2 V617F mutation (75.8 %), 3 patients type I CALR mutation (9.1%), 1 patient harbored W515K MPL mutation (3%), and 4 were triple negative (12.1%). Half of them incurred a MPN diagnosis antecedent (19/33, 57.6%) or synchronous (11/33, 33%) with MGUS diagnosis, while only 3 patients (9.1%) had MGUS diagnosed before MPN. Serum M protein consisted in a majority of IgG (84.8%, 14 cases ʎ e 14 ƙ light chain), 2 cases of IgA and 1 case of IgM protein with a median count of 1.04 plasma-cells in bone marrow aspirate at diagnosis. Eventually, after a median follow-up of 7 years (range 1-30 years), 5 patients (15.2%) originated a second hematological malignancy and 2 patients (6.1%) evolved in secondary myelofibrosis. In particular, 3 patients (10%) developed Non-Hodgkin lymphoma, 1 patient MM, and 1 patient developed acute myeloid leukemia (AML). NGS, cytogenetic, clinical history and MPN specific therapies don’t seem to influence clinical course of analyzed patients. Summary/Conclusion: In literature there are few publications that highlight the coexistence of MGUS in MPN patients. Currently little is known about the underlying molecular mechanisms and there are no guidelines clarifying whether a particular treatment or follow-up is necessary. The incidence of MGUS in our MPN cohort is higher than general population matched for sex and age. Although, this data can be influenced by an accurate hematological follow-up, we can’t exclude a real increased rate of MGUS in MPN patient. It is known MPN can predispose to an higher risk of developing second primary malignancies such as B cellular lymphoproliferative disorders. Interestingly, in our cohort the percentage of patients with coexisting MGUS and MPN who developed second hematological malignancies seemed slightly higher than literature data. Further studies with case-control cohort are necessary to better understand the possible prognostic impact and mutual influence between MPN and MGUS.