The impact of bone marrow fibrosis and JAK2 expression on clinical outcomes in patients with newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors

Cancer Med. 2020 Aug;9(16):5869-5880. doi: 10.1002/cam4.3265. Epub 2020 Jul 6.

Abstract

We determined the impact of bone marrow fibrosis (BMF) on the clinical outcomes of newly diagnosed multiple myeloma (NDMM) patients in the current era of myeloma therapy. A total of 393 MM patients were included in the final analysis. The median followup was 83 months (range: 3.9 to 212 months). BMF was noted in 122 (48.2%) evaluable patients. Median progression free survival (PFS) in patients without BMF was 30.2 (95% CI: 24.7-38.0) months, and 21.1 (95% CI: 18.8-27.5) months in patients with BMF present (P = .024). Median overall survival (OS) was 61.2 (95% CI: 51.5-81.2) months in patients without BMF, and 45.1 (95% CI: 38.7-57.0) months in patients with BMF (P = .0048). A subset of 99 patients had their bone marrow biopsies stained for JAK1 and JAK2 by immunohistochemistry. Of these samples 67 (67.7%) patients had detectable JAK2 expression predominantly noted on bone marrow megakaryocytes. JAK2 expression correlated with myeloma disease stage (P = .0071). Our study represents the largest dataset to date examining the association of BMF with prognosis in the era of novel therapies and widespread use of hematopoietic stem cell transplant (HSCT). Our data suggest that MM patients with BMF (particularly those with extensive BMF) have a poorer prognosis even when treated with immunomodulatory agents and proteasome inhibitors.

Keywords: JAK2; bone marrow fibrosis; immunohistochemical staining; multiple myeloma; overall survival; progression free survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Bone Marrow / chemistry
  • Bone Marrow / pathology
  • Confidence Intervals
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Immunologic Factors / therapeutic use*
  • Janus Kinase 1 / analysis
  • Janus Kinase 2 / analysis*
  • Male
  • Megakaryocytes / chemistry
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Primary Myelofibrosis / complications*
  • Primary Myelofibrosis / mortality
  • Prognosis
  • Progression-Free Survival
  • Proteasome Inhibitors / therapeutic use*
  • Retrospective Studies
  • Syndecan-1 / analysis
  • Treatment Outcome

Substances

  • Immunologic Factors
  • Proteasome Inhibitors
  • SDC1 protein, human
  • Syndecan-1
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2