High-risk myeloma and minimal residual disease postautologous-HSCT predict worse outcomes

Leuk Lymphoma. 2019 Feb;60(2):442-452. doi: 10.1080/10428194.2018.1485908. Epub 2018 Jul 22.

Abstract

The aim of our study was to determine the impact of high-risk disease (HRD) and MRD on outcomes in myeloma patients receiving bortezomib-based induction followed by autologous hematopoietic stem cell transplant (auto-HSCT). HRD included t(4:14), t(14;16), del 17p, del 1p and/or amplification 1q by cytogenetics/FISH; all others were standard-risk disease (SRD). A subset of 165 newly diagnosed myeloma patients in a 2:1 ratio of HRD:SRD was generated using propensity score based nearest neighbor matching. Multiparametric flow cytometry (MFC) was used to detect MRD after auto-HSCT in select patients. MRD+ status at 3 months post auto-HSCT (hazard ratio (HR = 4.23, p = .028) and HRD (HR = 1.72, p = .026) were associated with a shorter PFS. Similarly, MRD+ 3 months post auto-HSCT (HR = 6.93, p = .08) and HRD (HR = 3.54, p < .001) and were associated with a shorter OS. Despite bortezomib-based induction, upfront auto-HSCT, and use of maintenance therapy, PFS and OS remained worse in MRD+ and HRD patients.

Keywords: Multiple myeloma; autologous stem cell transplant; flow cytometry; high-risk cytogenetics; minimal residual disease; nearest neighbor matching.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Chromosome Aberrations
  • Combined Modality Therapy
  • Cytogenetic Analysis
  • Female
  • Flow Cytometry
  • Genetic Predisposition to Disease
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / etiology
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / therapy
  • Neoplasm, Residual / diagnosis*
  • Prognosis
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Biomarkers, Tumor