Clinical Outcome of Induction Treatment in the Era of Novel Agents and the Impact of the Number of High-Risk Cytogenetic Abnormalities (HRA) on Prognosis of Patients With Newly Diagnosed Multiple Myeloma (NDMM): Insights From a Multicenter Study

Cancer Med. 2024 Oct;13(20):e70270. doi: 10.1002/cam4.70270.

Abstract

Background: In the era of novel agents, the clinical outcomes of induction treatment and the impact of the number of high-risk cytogenetic abnormalities (HRA) in newly diagnosed multiple myeloma (NDMM) need to be explored.

Objective: Through this study, we aim to analyze the effectiveness of different induction treatments and explore the survival outcomes of patients with varying numbers of HRA.

Methods: A total of 734 patients from seven medical centers were included in our study.

Results: Patients in the CD38 monoclonal antibody or IMiDs plus proteasome inhibitors (PI) groups had significantly superior overall survival (OS) and progression-free survival (PFS) compared to those receiving IMiDs or PI alone. Additionally, the CD38 monoclonal antibody conferred a PFS advantage over IMiDs plus PI. Patients with ≥ 2 high-risk cytogenetic abnormalities (HRA) exhibited an extremely poor prognosis and should be considered ultra-high-risk individuals in multiple myeloma (MM). The CD38 monoclonal antibody, transplantation, and achieving minimal residual disease (MRD) negativity only partly mitigated the poor prognosis in patients with HRA. Furthermore, patients with 1q21 gain/amplification (1q21+) only had a significantly worse prognosis compared to patients without HRA, and those with 1q21+ plus del17p or t(4;14) exhibited an inferior prognosis compared to those with 1q21+ alone.

Conclusion: Our results suggested that double-hit multiple myeloma was associated with extremely poor survival outcomes, and more effective treatments needed to be explored for this particular subtype of MM.

Keywords: 1q21 gain/amplification; CD38; high risk cytogenetic abnormalities; newly diagnosed multiple myeloma.

Publication types

  • Multicenter Study

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chromosome Aberrations*
  • Female
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / pathology
  • Multiple Myeloma* / therapy
  • Prognosis
  • Progression-Free Survival
  • Proteasome Inhibitors / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Proteasome Inhibitors
  • ADP-ribosyl Cyclase 1