Clinical and molecular characteristics of lymphoplasmacytic lymphoma not associated with an IgM monoclonal protein: A multicentric study of the Rete Ematologica Lombarda (REL) network

Am J Hematol. 2019 Nov;94(11):1193-1199. doi: 10.1002/ajh.25600. Epub 2019 Sep 9.

Abstract

Lymphoplasmacytic lymphoma (LPL) is usually associated with a serum IgM paraprotein, corresponding to Waldenström's Macroglobulinemia (WM). Cases presenting with IgG or IgA, or without a monoclonal protein are extremely rare. We analyzed clinical characteristics, frontline treatment, and the outcome of 45 patients with non-IgM LPL, and compared them with a control group of WM patients. The median age was similar, with significantly higher prevalence of females in non-IgM LPL, than in WM patients (60% vs 39%, P = .016). Patients with non-IgM LPL more frequently presented with lymphadenopathies (53% vs 15%, P < .001), splenomegaly (22% vs 8%, P = .015) or extranodal involvement (20% vs 8%, P = .05). In non-IgM LPL a serum monoclonal protein and bone marrow infiltration were less common than in WM patients (69% and 84% of cases respectively, P < .001 for both comparisons). The MYD88 (L265P) mutation was found in 8/19 patients using allele-specific polymerase chain reaction. A CXCR4 mutation was found in 4/17 cases using Sanger. In 16 patients we performed targeted next-generation sequencing of genes MYD88, CXCR4, ARID1-A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, TNFAIP3. Seven patients (44%) had a MYD88 mutation (S219C in one), four (25%) a CXCR4 mutation, three (19%) a KMT2D mutation, one (6%) a TP53 mutation and one (6%) a TRAF3 mutation. With a median follow-up of 55.7 months, 36 non-IgM LPL patients (80%) were treated. Non-IgM LPL patients received more frequently anthracycline-containing regimens, as compared with WM patients, who mainly received alkylating-based therapies. Five-year overall survival (OS) was 84%, similar to that of WM patients.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / administration & dosage
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Mutation
  • Myeloid Differentiation Factor 88 / genetics
  • Neoplasm Proteins / genetics
  • Paraproteins / analysis*
  • Progression-Free Survival
  • Receptors, CXCR4 / genetics
  • Sex Distribution
  • Waldenstrom Macroglobulinemia / blood
  • Waldenstrom Macroglobulinemia / drug therapy
  • Waldenstrom Macroglobulinemia / epidemiology*
  • Waldenstrom Macroglobulinemia / genetics

Substances

  • Anthracyclines
  • Antineoplastic Agents, Alkylating
  • CXCR4 protein, human
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Neoplasm Proteins
  • Paraproteins
  • Receptors, CXCR4