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<p>Measurable residual disease (MRD) assessment has become central to risk-adapted treatment strategies in multiple myeloma, yet the prognostic value of MRD negativity following autologous stem cell transplantation (ASCT) across individual high-risk cytogenetic abnormalities (HRCAs) remains unclear. We analyzed 351 newly diagnosed patients who achieved MRD negativity (sensitivity 2.4 × 10<sup>−6</sup>) between day 60-100 following ASCT and had baseline cytogenetic data available. Median follow-up was 50.4 months. Standard-risk cytogenetics were present in 46% (<i>n</i> = 162), while 34% (<i>n</i> = 118) had one HRCA and 20% (<i>n</i> = 71) had ≥2 HRCAs. Despite uniform MRD negativity, several HRCAs continued to confer inferior progression-free survival (PFS). Compared with the standard-risk group (4-year PFS 84%), patients with del(17p), 1q21+, t(4;14), or MAF translocations [t(14;16)/t(14;20)] had significantly lower 4-year PFS rates: 56% (HR 2.89; <i>p</i> = 0.0001), 60% (HR 2.46; <i>p</i> = 0.0001), 43% (HR 3.50; <i>p</i> = 0.0001), and 58% (HR 2.51; <i>p</i> = 0.01), respectively. Isolated del(17p) and 1q21+ also conferred inferior PFS. The 4-year PFS was 65% for patients with one HRCA (HR 2.31; <i>p</i> = 0.0004) and 55% for those with ≥2 HRCAs (HR 2.75; <i>p</i> = 0.0001). In this large MRD-negative post-ASCT cohort, several HRCAs, including isolated HRCAs, were associated with inferior PFS, suggesting a potential persistence of high-risk biology despite early MRD negativity.</p>

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Cytogenetics-based clinical trajectories in patients with MRD negativity post autologous transplant for multiple myeloma

  • 期刊论文

  • 发表日期：

    2026年7月21日

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  • Estefania Gauto Mariotti,
  • Shaji Kumar,
  • Wilson Gonsalves,
  • Prashant Kapoor,
  • Francis Buadi,
  • Suzanne Hayman,
  • Nadine Abdallah,
  • Moritz Binder,
  • Joselle Cook,
  • Angela Dispenzieri,
  • David Dingli,
  • Morie A. Gertz,
  • Taxiarchis Kourelis,
  • Nelson Leung,
  • Yi Lin,
  • Mustaqeem Siddiqui,
  • Ronald Go,
  • Eli Muchtar,
  • Rahma Warsame,
  • Dragan Jevremovic,
  • Robert A. Kyle,
  • S. Vincent Rajkumar,
  • Saurabh Zanwar

摘要

Measurable residual disease (MRD) assessment has become central to risk-adapted treatment strategies in multiple myeloma, yet the prognostic value of MRD negativity following autologous stem cell transplantation (ASCT) across individual high-risk cytogenetic abnormalities (HRCAs) remains unclear. We analyzed 351 newly diagnosed patients who achieved MRD negativity (sensitivity 2.4 × 10−6) between day 60-100 following ASCT and had baseline cytogenetic data available. Median follow-up was 50.4 months. Standard-risk cytogenetics were present in 46% (n = 162), while 34% (n = 118) had one HRCA and 20% (n = 71) had ≥2 HRCAs. Despite uniform MRD negativity, several HRCAs continued to confer inferior progression-free survival (PFS). Compared with the standard-risk group (4-year PFS 84%), patients with del(17p), 1q21+, t(4;14), or MAF translocations [t(14;16)/t(14;20)] had significantly lower 4-year PFS rates: 56% (HR 2.89; p = 0.0001), 60% (HR 2.46; p = 0.0001), 43% (HR 3.50; p = 0.0001), and 58% (HR 2.51; p = 0.01), respectively. Isolated del(17p) and 1q21+ also conferred inferior PFS. The 4-year PFS was 65% for patients with one HRCA (HR 2.31; p = 0.0004) and 55% for those with ≥2 HRCAs (HR 2.75; p = 0.0001). In this large MRD-negative post-ASCT cohort, several HRCAs, including isolated HRCAs, were associated with inferior PFS, suggesting a potential persistence of high-risk biology despite early MRD negativity.