Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, MAIA
Michele Cavo 1 , Jesus F F San-Miguel 2 , Saad Z Usmani 3 , Katja C Weisel 4 , Meletios A A Dimopoulos 5 , Hervé Avet-Loiseau 6 , Bruno Paiva 7 , Nizar J Bahlis 8 , Torben Plesner 9 , Vania Tietsche de Moraes Hungria 10 , Philippe Moreau 11 , Maria Victoria Mateos 12 , Aurore Perrot 13 , Shinsuke Iida 14 , Thierry Facon 15 , Shaji K Kumar 16 , Niels W C J van de Donk 17 , Pieter Sonneveld 18 , Andrew Spencer 19 , Maria Krevvata 20 , Christoph Heuck 20 , Jianping Wang 21 , Jon Ukropec 22 , Rachel Kobos 23 , Steven Sun 23 , Mia Qi 24 , Nikhil C Munshi 25
We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM) using data from four 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 versus standards of care.
We conducted a large-scale pooled analysis for associations between patients achieving complete response (CR) or better with MRD-negative status, and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10‒5 threshold).
Patient-level data were pooled from all four studies, and for patients with TIE NDMM plus patients with RRMM who received ≤2 prior lines of therapy (≤2PL). PFS was evaluated by response and MRD status. Median follow-up (months) was: POLLUX, 54.8; CASTOR, 50.2; ALCYONE, 40.1; and MAIA, 36.4. Patients who achieved ≥CR and MRD negativity had improved PFS versus 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 ≤2PL 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 www.ClinicalTrials.gov: NCT02076009/NCT02136134/NCT02195479/NCT02252172.
CITA DEL ARTÍCULO Blood. 2021 Jul 21;blood.2021011101. doi: 10.1182/blood.2021011101