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MULTIPLE MYELOMA, GAMMOPATHIES

The impact of high-risk cytogenetics on treatment efficacy and outcomes of patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis of randomized controlled trials

Leukemia volume 39, pages 2226–2236 (2025)Cite this article

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Abstract

The cytogenetic abnormalities translocations t(4;14) and t(14;16) and the deletion of chromosome 17p in newly-diagnosed multiple myeloma are associated with poor disease prognosis and are traditionally deemed as “high-risk”. However, in the setting of relapsed/refractory multiple myeloma (RRMM) their effect is less characterized. A systematic search was conducted in the PubMed database (end-of-search: 20 August 2024) for randomized controlled trials on anti-myeloma therapies for RRMM that reported outcomes for standard-risk and high-risk patient subgroups. A total of 28 studies were included; 23 reported progression-free survival (PFS) and 8 overall survival (OS) outcomes. Per overall analysis, high-risk cytogenetics were not associated with impaired treatment efficacy compared to standard-risk in terms of both PFS and OS. Among 9 treatment subgroups, high-risk patients on anti-BCMA therapies seemed to exhibit a 18% lower risk of a PFS event compared to the overall treatment effect for this population, but results were not significant. In the subgroup analyses, deletion 17p seemed to have the biggest impact on treatment efficacy, but results were not statistically significant. Overall, the presence of high-risk cytogenetics at study entry in RRMM did not alter treatment efficacy. Novel tools are needed to improve risk stratification at myeloma relapse.

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Fig. 1: Flow diagram for the succesive steps in the selection of studies.
Fig. 2: Pooled estimates of PFS HR (experimental arm vs control arm), by treatment subgroup.
Fig. 3: Pooled estimates of OS HR (experimental arm vs control arm), by treatment subgroup.

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Data availability

Data available upon request from the corresponding author.

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Author notes

  1. These authors contributed equally: Ioannis Ntanasis-Stathopoulos, Charalampos Filippatos.

Authors and Affiliations

  1. Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Ioannis Ntanasis-Stathopoulos, Charalampos Filippatos, Panagiotis Malandrakis, Efstathios Kastritis, Evangelos Terpos, Meletios-Athanasios Dimopoulos & Maria Gavriatopoulou

  2. First Department of Radiology, School of Medicine, Areteion Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Vassilis Koutoulidis

  3. Laboratory of Chemistry, Biochemistry and Cosmetic Science, Department of Biomedical Medicine, University of West Attica, Egaleo, Greece

    Maria Trapali

  4. Department of Medicine, Korea University, Seoul, South Korea

    Meletios-Athanasios Dimopoulos

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Contributions

Conceptualization: INS, CF, MG; Data curation: INS, CF, PM; Formal analysis: CF; Investigation: INS, PM, VK, MT, EK, ET, MAD, MG; Methodology: INS, CF; Supervision: ET, MG; Roles/Writing - original draft: INS, CF; Writing - review & editing: PM, VK, MT, EK, MAD, ET, MG.

Corresponding author

Correspondence to Maria Gavriatopoulou.

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Competing interests

INS declares honoraria from Janssen. PM declares honoraria from Janssen. EK declares honoraria from Amgen, Janssen, GSK, and Pfizer. MAD declares honoraria from Abbvie, Amgen, Bristol Myers Squibb, GSK, Janssen, Karyopharm, Pharmacyclics Inc, Pfizer, Sanofi, and Takeda. ET declares honoraria from Amgen, Astra/Zeneca, Bristol Myers Squibb, Eusa Pharma, GSK, Integris Pharma, Janssen, Pfizer, Sanofi, and Takeda. MG declares honoraria from GSK, Janssen, Sanofi, Abbvie, Amgen, and Takeda. The other authors declare no conflict of interest.

Ethics approval and consent to participate statement

This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. As this study is based solely on previously published peer-reviewed data and does not involve human participants, interventions, or identifiable personal data, it did not require approval by an ethics committee or informed consent.

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Ntanasis-Stathopoulos, I., Filippatos, C., Malandrakis, P. et al. The impact of high-risk cytogenetics on treatment efficacy and outcomes of patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis of randomized controlled trials. Leukemia 39, 2226–2236 (2025). https://doi.org/10.1038/s41375-025-02677-5

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