Presentation and Impact of Double and Triple hit Cytogenetics in Patients With Multiple Myeloma in the Real World

Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):e685-e690. doi: 10.1016/j.clml.2022.03.005. Epub 2022 Mar 19.

Abstract

Introduction: The presence of 2 or more high-risk cytogenetic abnormalities on FISH characterizes patients as Double/Triple Hit Myeloma (DH/THM). This entity has poorer outcomes, though data from the real-world setting is scarce.

Patients and methods: We retrospectively analyzed all MM patients presenting to our hospital over 3 years to study the clinical characteristics and outcomes with DH/THM.

Results: Fifty-five (19.2%) of 285 newly-diagnosed MM patients had DH/THM. The most common cytogenetic abnormality was increased copies of chromosome 1q (53 patients, 96.4%)- 22 patients had 3 copies, and 31 patients had 4 or more copies. The most common cytogenetic combination was IgH-FGFR3 translocation, increasing 1q copy number (28 patients; 50.9%). The disease was characterized by aggressive presentation, with 9 patients (16.4%) dying in the first month after diagnosis, and 7 patients (12.7%) dying in the second month. Only 22 patients (40%) achieved a VGPR or better with therapy. The Median EFS and OS for the cohort were 8 months and thirteen months, respectively. On multi-variate analysis, renal failure and plasma cell leukemia were associated with increased mortality risk, while achievement of VGPR or better was associated with better survival.

Conclusion: Our findings suggest that multiple myeloma patients with double/triple hit cytogenetics on FISH have aggressive presentations, high early mortality, and poor outcomes. These patients may benefit from more aggressive regimens and better supportive care.

Keywords: Double-hit; Early mortality; Global Oncology; Real-world data; Ultra-high risk.

MeSH terms

  • Chromosome Aberrations*
  • Cytogenetic Analysis
  • Cytogenetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Multiple Myeloma* / diagnosis
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Prognosis
  • Retrospective Studies