Background: The role of MRD by MFC and NGS is well known in MM, with few data on the concordance of the two techniques. We analyzed and compared MRD data from the FORTE trial both by MFC and NGS. Methods: Newly diagnosed MM patients (pts) ≤65 years were randomized to: carfilzomib, lenalidomide, dexamethasone (KRd) induction-autologous stem cell transplant (ASCT) - KRd consolidation (KRd_ASCT); 12 KRd cycles (KRd12); carfilzomib, cyclophosphamide, dexamethasone (KCd) induction-ASCT-KCd consolidation (KCd_ASCT). Pts were then randomized to maintenance: lenalidomide alone or plus carfilzomib. MRD was assessed by 8-color second generation flow cytometry (sensitivity 10⁻⁵) in pts with ≥very good partial response (VGPR) before maintenance. In a subgroup of these pts, next generation flow (NGF; sensitivity 10⁻⁵-10⁻⁶) was performed. In ≥CR pts, MRD pre-maintenance was also assessed by NGS (Adaptive Biotechnologies; sensitivity 10⁻⁵-10⁻⁶). Thus, both MFC and NGS evaluations were available only in ≥CR pts. 1-year sustained MRD negativity by MFC and NGS was also analyzed in pts with at least one sample available at least 1 year apart. Results: MFC and NGS data were available in 184/233 (79%) CR pts (66 KRd_ASCT, 67 KRd12 and 51 KCd_ASCT). Median age of this ≥CR population was 57 years (IQR 52-62), 13% had International Staging System (ISS) III and 27% high risk cytogenetics by FISH [either del(17p) or t(4;14) or t(14;16)]. Table reports MRD negativity rate by MFC and NGS at a cut-off of 10⁻⁵ and 10⁻⁶ among ≥CR negative pts in the 3 arms. NGS negativity at a cut-off 10⁻⁶ was found in 36/133 (27%) ≥CR pts (for 51/184 CR pts 10⁻⁶ sensitivity was not reached). In evaluable pts, 1-year sustained 10⁻⁵ MRD negativity by MFC and NGS was superimposable (83%). We evaluated concordance of MRD results by the two techniques and observed agreement was 86% for MFC and NGS at 10⁻⁵ evaluable samples (n: 335; r: 0.61) and 78% for MFC and NGS at 10⁻⁶ evaluable samples (n: 56; r: 0.77). Conclusions: In pts who achieved ≥CR, similar rate of pre-maintenance 10⁻⁵ negativity by MFC and NGS has been reached in each arm, with 83% pts maintaining 1-year MFC or NGS 10⁻⁵ sustained MRD negativity. Concordance between MFC and NGS was good, particularly when the same sensitivity was reached. Longer follow up is needed to draw definitive conclusions. Clinical trial information: NCT02203643.

*calculated on NGS 10⁻⁶ evaluable pts