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<p>Risk stratification models based on cytogenetics and disease burden help identify high-risk patients with newly diagnosed multiple myeloma (NDMM). However, some high-risk patients remain undetected. This study evaluated the prognostic utility of the proportion of clonal plasma cells in the S-phase of the cell cycle for NDMM. Patients with active multiple myeloma diagnosed between 01/01/2013 and 01/31/2023 who underwent S-phase assessment were included. The S-phase proportion was calculated by analyzing DNA content between G0/G1 and G2/M peaks. Among 823 patients, 16% (135) had S-phase ≥2% at diagnosis. Patients with S-phase ≥2% exhibited significantly worse median progression-free survival (PFS) of 1.4 years (95% CI: 1.2–1.9) compared to 2.9 years (95% CI: 2.6–3.3) for those with S-phase &lt;2% (HR 1.6, <i>p</i> &lt; 0.0001). Median overall survival (OS) was also significantly lower at 3.9 years (95% CI: 2.9–5.7) versus 9.2 years (95% CI: 7.9–not reached; HR 2.2, <i>p</i> &lt; 0.0001). Multivariate analysis confirmed S-phase ≥2% as an independent predictor of inferior PFS (HR 1.56, <i>p</i> = 0.001) and OS (HR 2, <i>p</i> &lt; 0.0001) after adjusting for R2-ISS risk, age, renal function, and treatment strategies. Among patients with S-phase ≥2%, 53% (68/129) experienced progression-free survival (PFS) under 18 months with upfront therapy. Elevated S-phase was associated with a 2.5-fold higher risk of progression within 18 months [OR 2.55 (95% CI: 1.7–3.7), <i>p</i> &lt; 0.001]. Patients with elevated S-phase but no IMS-high risk had a median OS of 5.7 years (95% CI: 4.7–9.2), similar to the IMS-high risk cohort without elevated S-phase (5.4 years, 95% CI: 4–NR). Those with both elevated S-phase and IMS-high risk had significantly worse OS (3.1 years, 95% CI: 1.6–NR, <i>p</i> = 0.043). These findings suggest that S-phase ≥2% is a powerful, independent prognostic marker for NDMM.</p>

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Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma

  • 期刊论文

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  • 发表日期：

    2025年2月18日

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  • Saurabh Zanwar,
  • Dragan Jevremovic,
  • Prashant Kapoor,
  • Horatiu Olteanu,
  • Francis Buadi,
  • Pedro Horna,
  • Wilson Gonsalves,
  • Gregory Otteson,
  • Abiola Bukunmi Bolarinwa,
  • Suzanne Hayman,
  • Nadine Abdallah,
  • Moritz Binder,
  • Joselle Cook,
  • Angela Dispenzieri,
  • David Dingli,
  • Morie A. Gertz,
  • Taxiarchis Kourelis,
  • Nelson Leung,
  • Yi Lin,
  • Eli Muchtar,
  • Rahma Warsame,
  • Amie Fonder,
  • Miriam Hobbs,
  • Yi Lisa Hwa,
  • Michelle Rogers,
  • Robert A. Kyle,
  • S. Vincent Rajkumar,
  • Shaji Kumar

摘要

Risk stratification models based on cytogenetics and disease burden help identify high-risk patients with newly diagnosed multiple myeloma (NDMM). However, some high-risk patients remain undetected. This study evaluated the prognostic utility of the proportion of clonal plasma cells in the S-phase of the cell cycle for NDMM. Patients with active multiple myeloma diagnosed between 01/01/2013 and 01/31/2023 who underwent S-phase assessment were included. The S-phase proportion was calculated by analyzing DNA content between G0/G1 and G2/M peaks. Among 823 patients, 16% (135) had S-phase ≥2% at diagnosis. Patients with S-phase ≥2% exhibited significantly worse median progression-free survival (PFS) of 1.4 years (95% CI: 1.2–1.9) compared to 2.9 years (95% CI: 2.6–3.3) for those with S-phase <2% (HR 1.6, p < 0.0001). Median overall survival (OS) was also significantly lower at 3.9 years (95% CI: 2.9–5.7) versus 9.2 years (95% CI: 7.9–not reached; HR 2.2, p < 0.0001). Multivariate analysis confirmed S-phase ≥2% as an independent predictor of inferior PFS (HR 1.56, p = 0.001) and OS (HR 2, p < 0.0001) after adjusting for R2-ISS risk, age, renal function, and treatment strategies. Among patients with S-phase ≥2%, 53% (68/129) experienced progression-free survival (PFS) under 18 months with upfront therapy. Elevated S-phase was associated with a 2.5-fold higher risk of progression within 18 months [OR 2.55 (95% CI: 1.7–3.7), p < 0.001]. Patients with elevated S-phase but no IMS-high risk had a median OS of 5.7 years (95% CI: 4.7–9.2), similar to the IMS-high risk cohort without elevated S-phase (5.4 years, 95% CI: 4–NR). Those with both elevated S-phase and IMS-high risk had significantly worse OS (3.1 years, 95% CI: 1.6–NR, p = 0.043). These findings suggest that S-phase ≥2% is a powerful, independent prognostic marker for NDMM.