Outcome prediction by interim positron emission tomography and IgM monoclonal gammopathy in diffuse large B-cell lymphoma

Abstract

In diffuse large B-cell lymphoma (DLBCL), a positive interim positron emission tomography (PET) scan predicts treatment failure, but the proportion of high-risk patients thus identified is small. To improve prediction, we combined the interim PET result with the presence or absence of an associated IgM gammopathy. Of 108 DLBCL patients participating in a prospective trial, nine (8%) were interim PET positive and 19 (18%) had an IgM gammopathy. The monoclonal protein was not associated with distinguishing genetic features, and its light chain restriction was not always concordant with the light chain restriction of the lymphoma. The information provided by interim PET and IgM gammopathy was combined to dichotomize the population into sizeable high-risk (1–2 adverse factors) and low-risk groups (no adverse factor) with widely different outcomes (population size, 25% vs. 75%; 3-year risk of progression, 51% vs. 10%; 3-year overall survival, 64% vs. 95%). Multivariable analyses including established risk factors revealed the interim PET result and the IgM gammopathy status to be the only factors significantly associated with outcome. Information about interim PET response and IgM gammopathy may be useful in studies testing risk-adapted treatment strategies.

Serum Paraprotein Is Associated with Adverse Prognostic Factors and Outcome, across Different Subtypes of Mature B-Cell Malignancies—A Systematic Review

“…In DLBCL, only the IgM PP has been reported, by almost all authors from the western world, to be a strong prognostic factor, independent from the IPI score, for both PFS and OS [ 33 , 34 , 35 , 36 , 38 ] Noteworthy, Cox et al, reported the detection of recurrent mutations in high impact genes, and the preferential IGVH4-34 gene usage, which allowed them to hypothesize that most IgMs-DLBCL originate from immune-escaped autoreactive B-cells [ 36 ]. Indeed, this feature [ 59 ] may also explain the high rate of CNS spreading [ 35 , 36 , 38 ]. Conversely, Johansson et al [ 38 ] found no prevalence of specific gene mutations and of the ABC-type.…”

“…Indeed, this feature [ 59 ] may also explain the high rate of CNS spreading [ 35 , 36 , 38 ]. Conversely, Johansson et al [ 38 ] found no prevalence of specific gene mutations and of the ABC-type. Therefore, more studies are necessary to shed light on the molecular correlatives and the etiopathogenesis of the IgMs-DLBCL subset.…”

“…Indeed, it is currently unknown if also the latter condition negatively impacts patient’s features and prognosis. In fact, some authors speculated that this status, as well as the detection of elevated free-light chains, may reflect immune-dysregulation of the host, which adversely affects patient’s outcome [ 12 , 38 , 43 ]. Definetely, to confirm that a paraprotein is secreted by the neoplasia, the heavy and light chains, expressed by the malignant B-cell, also need to be characterized.…”

“…Fifteen 15 IgM+ve cases were analyzed for gene mutations and COO. However, results failed to show the prevalence of the ABC-type and of MYD88 and TP53 genes’ mutations [ 38 ].…”