Deepening of response after completing rituximab-containing therapy in patients with Waldenstrom macroglobulinemia

Am J Hematol. 2020 Apr;95(4):372-378. doi: 10.1002/ajh.25712. Epub 2020 Jan 7.

Abstract

Rituximab-containing regimens are commonly used for frontline therapy in patients with symptomatic Waldenström macroglobulinemia (WM). We had observed that a portion of WM patients experienced deepening of response months to years after therapy completion. We carried a retrospective study aimed at describing this phenomenon. We gathered baseline data, and responses at end of induction, end of maintenance and best response. Deepening of response was defined as ≥25% decrease in serum IgM achieved at a later time from therapy completion. Of 178 patients included, 116 (65%) received maintenance therapy and 62 (35%) were observed. In patients who received maintenance, 44 (38%) had ≥25% decrease in serum IgM level after the end of maintenance with a median time from end of maintenance to lowest IgM level of 1.6 years (range 0.1-7.9 years). In patients who were observed, 19 (31%) had ≥25% decrease in serum IgM level after the end of induction with a median time from end of induction to lowest IgM level of 1.6 years (range 0.2-5.1 years). Baseline hemoglobin <11.5 g/dL, bone marrow involvement ≥50%, CXCR4 mutations and serum IgM ≥4000 mg/dL were associated with lower odds of deepening of response after therapy completion. Deepening of response was associated with better progression-free survival (PFS; HR 0.46, 95% CI 0.26-0.80; P = .006) and better survival after frontline treatment initiation (SAFTI; HR 0.21, 95% CI 0.06-0.73; P = .01). In conclusion, deepening of response occurs in one third of WM patients after completing rituximab-containing regimens and was associated with better PFS and SAFTI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin M / blood
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Myeloid Differentiation Factor 88 / genetics
  • Paraproteins / analysis
  • Progression-Free Survival
  • Receptors, CXCR4 / genetics
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Survival Analysis
  • Waldenstrom Macroglobulinemia / blood
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / genetics
  • Waldenstrom Macroglobulinemia / pathology

Substances

  • CXCR4 protein, human
  • Immunoglobulin M
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Paraproteins
  • Receptors, CXCR4
  • Rituximab