Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA

Michele Cavo, Jesus San-Miguel, Saad Z. Usmani, Katja Weisel, Meletios A. Dimopoulos, Hervé Avet-Loiseau, Bruno Paiva, Nizar J. Bahlis, Torben Plesner, Vania Hungria, Philippe Moreau, Maria Victoria Mateos, Aurore Perrot, Shinsuke Iida, Thierry Facon, Shaji Kumar, Niels W.C.J. van de Donk, Pieter Sonneveld, Andrew Spencer, Maria KrevvataChristoph Heuck, Jianping Wang, Jon Ukropec, Rachel Kobos, Steven Sun, Mia Qi, Nikhil Munshi

Research output: Contribution to journalArticlepeer-review


We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) using data from 4 phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD negativity rates and reduced the risk of disease progression or death by approximately half vs standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response or better (≥CR) with MRD-negative status and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10−5 sensitivity threshold). Patient-level data were pooled from all 4 studies and for patients with TIE NDMM and patients with RRMM who received ≤2 prior lines of therapy (≤2 PL). PFS was evaluated by response and MRD status. Median follow-up (months) was 54.8 for POLLUX, 50.2 for CASTOR, 40.1 for ALCYONE, and 36.4 for MAIA. Patients who achieved ≥CR and MRD negativity had improved PFS vs those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P <.0001; TIE NDMM and RRMM ≤2 PL HR 0.20, P <.0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that ≥CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching ≥CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support ≥CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM. These trials were registered at as #NCT02076009, #NCT02136134, #NCT02195479, and #NCT02252172.

Original languageEnglish (US)
Pages (from-to)835-844
Number of pages10
Issue number6
StatePublished - Feb 10 2022

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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