Abstract
Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p = .002) stage III-IV(p = .003), ≥2 extra nodal sites (p<.0001), bone-marrow (p = .002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3–5 (p = .009) and failure to achieve complete remission (p = .005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p = .005, expB = 0.339, CI = 0.160-0.716) and IPI-score 3–5 (p = .010, expB = 0.274, CI = 0.102–0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immmunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement.
Highlights
Diffuse-Large-B-cell Lymphoma (DLBCL) is a biologically heterogeneous entity [1],that is still homogeneously treated with Rituximab-Cyclophosphamide-Adriamycin-Vincristine-Prednisone (R-CHOP) immunochemotherapy [2]
After 1-3 cycles of R-CHOP the monoclonal IgM component disappeared and the free light chain (FLC) k/l ratio returned to the normal range in all of these patients
Several prognostic factors and scores have been proposed to better stratify patients who would benefit from more intensive treatment than R-CHOP [5,10,11]
Summary
Diffuse-Large-B-cell Lymphoma (DLBCL) is a biologically heterogeneous entity [1],that is still homogeneously treated with Rituximab-Cyclophosphamide-Adriamycin-Vincristine-Prednisone (R-CHOP) immunochemotherapy [2]. Since considerable efforts have been made in order to translate the complexity of GEP-derived information into fewer data readily achievable by routine tests. This attempt is still in progress [6], and the choice of shifting towards an upfront intensified treatment remains largely based on the IPI-score or on IPI-derived scores [7,8]. In this study we have further increased and characterized a series of DLBCL with an associated IgM MC [18], reporting detailed analysis of their clinical, histological and molecular features
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