Familial disease predisposition impacts treatment outcome in patients with Waldenström macroglobulinemia

Clin Lymphoma Myeloma Leuk. 2012 Dec;12(6):433-7. doi: 10.1016/j.clml.2012.08.006. Epub 2012 Oct 17.

Abstract

Familial disease is common in Waldenström macroglobulinemia (WM). We examined the impact of familial disease status on treatment outcome in WM and observed that familial disease was associated with inferior outcomes. However patients with familial WM receiving a bortezomib-containing regimen showed improved treatment outcomes vs. those receiving non–bortezomib-containing regimens. Bortezomib-containing regimens may therefore represent a more optimal treatment approach for patients with familial WM.

Background: We examined the impact of familial predisposition on treatment outcome in 135 patients with Waldenström macroglobulinemia (WM), 26.7% of whom had first- or second-degree relatives with a B-cell lymphoproliferative disorder.

Patients and methods: All patients were rituximab naive and received a rituximab-containing regimen. There were no significant differences in baseline characteristics between cohorts.

Results: Overall response (93.9% vs. 75.0%; P = .029) and complete response/very good partial response (CR/VGPR) (23.2% vs. 16.7%; P < .0001), time to progression (TTP) (45.5 vs. 21 months; P = .015) and time to next therapy (TTNT) (50.0 vs. 33.0 months; P = .024) favored patients with sporadic WM. By multivariate analysis, familial predisposition was an independent marker for disease progression (hazard ratio, 0.554). Patients with familial but not sporadic disease exhibited better responses, including CR/VGPR attainment (P = .0006) and a trend for longer progression-free survival (> 33 vs. 20.6 months; P = .08), with bortezomib-containing therapy.

Conclusion: The findings convey that familial predisposition is an important determinant of treatment outcome in WM. Prospective studies to confirm these observations are needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / genetics*

Substances

  • Boronic Acids
  • Pyrazines
  • Bortezomib
  • Cyclophosphamide
  • Vidarabine
  • fludarabine