PB2009 PERIPHERAL BLOOD INVOLVEMENT BY FLOW CYTOMETRY IS NOT AN UNUSUAL FEATURE IN IGM MGUS/WALDENSTRÖM MACROGLOBULINEMIA WITH MYD88 L265P MUTATION.

Background: The IgM monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum IgM paraprotein concentration <30 g/L, bone marrow (BM) lymphoplasmacytic infiltration by clonal population <10% and no symptoms or end‐organ damage. Waldenström Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma (LPL) with BM involvement and an IgM monoclonal gammopathy of any concentration. Patients fullfilling criteria for WM and not requiring inmediate treatment are classified as smoldering WM. More than 90% of LPL/WM cases and 60% of IgM MGUS display the MYD88 L265P mutation ( MYD88 mut), suggesting that IgM MGUS is closer to mature B‐cell neoplasms than to plasma cell myeloma according to 2016 WHO update. From the immunophenotypic point of view, clonal B cells are reported in 75% of IgM MGUS in BM on multiparameter flow cytometry (FC). However, data about peripheral blood (PB) involvement in IgM MGUS/WM are scarce. Aims: To analyze the incidence of PB involvement detected by FC in a series of IgM MGUS/WM with MYD88 mut in BM consecutively diagnosed in a single institution. Methods: 69 patients (47 male/22 female; median age 77 years, range 38‐92) diagnosed with IgM MGUS/WM MYD88 mut between 2000 and 2019 with PB FC availability were selected. The diagnosis was made in BM in all cases. For FC analysis, 100,000 events were acquired in a FACSCanto II (BD) cytometer and were analyzed with the Infinicyt software (Cytognos). The study of the MYD88 L265P mutation was performed in PB by allele‐specific qPCR and the analysis of the IGH gene rearrangement by PCR. Results: Monoclonal gammopathy was detected in routine blood tests in asymptomatic patients in 52/69 (75%) cases. Median lymphocyte count was 2.04x10 9 /L (0.77‐8.81). Only 3/69 (4.3%) patients presented with ≥4x10 9 /L lymphocytes. Leukemic involvement by FC was detected in 36/69 (52%) patients (see Table 1). The phenotype of clonal lymphocytes was the usually described in WM (CD19dimCD22dimCD25dim) in most cases. In those patients, the median percentage of B‐cells from the total lymphocytes was 8% (0.6‐40%) with only 5 (7%) patients presenting ≥20% B‐lymphocytes. The median percentage of clonal B‐cells in respect of the total number of B‐cells was 60% (3‐100%). However, in 9 patients the clonal B‐lymphocytes could not be quantified because of the minor representation of this abnormal population with non‐specific phenotype. In 5 (7%) patients an additional abnormal B‐cell population was detected, 4/5 being phenotypically consistent with chronic lymphocytic leukemia. PB involvement was most frequently observed in patients displaying ≥30% lymphocytes in BM (15/20, 75% vs. 21/48, 44% in patients with <30% lymphocytes, P  = 0.032). No differences were observed with regard to the amount of serum monoclonal component (PB involvement: 12/24 cases with ≥15 g/L vs. 24/45 patients with <15 g/L, P  = NS). MYD88 mut was detected in 31/34 (91%) cases with leukemic expression. In 13/31 (42%) patients without PB involvement by FC, molecular data were consistent with circulating disease (only MYD88 mut 2/31, only clonal IGH rearrangement 5/29, both 6/29). Summary/Conclusion: In our series, PB involvement by FC was not unusual in patients with IgM MGUS/MW MYD88 mut. However, nearly all patients had a normal lymphocyte count and a percentage of B‐cells within the normal ranges. Leukemic expression by FC correlated with the degree of BM infiltration. Finally, PB involvement could be detected by molecular techniques ( MYD88 L265P mutation and/or clonal IGH rearrangement) in almost half of the patients with negative FC.