The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements

Abstract

Background Stringent complete response (sCR) is used as a deeper response category than complete response (CR) in multiple myeloma (MM) but may be of limited value in the era of minimal residual disease (MRD) testing. Methods Here, we used 4-colour multiparametric flow cytometry (MFC) or next-generation sequencing (NGS) of immunoglobulin genes to analyse and compare the prognostic impact of sCR and MRD monitoring. We included 193 treated patients in two institutions achieving CR, for which both bone marrow aspirates and biopsies were available. Results We found that neither the serum free light chain ratio, clonality by immunohistochemistry (IHC) nor plasma cell bone marrow infiltration identified CR patients at distinct risk. Patients with sCR had slightly longer progression-free survival. Nevertheless, persistent clonal bone marrow disease was detectable using MFC or NGS and was associated with significantly inferior outcomes compared with MRD-negative cases. Conclusion Our results confirm that sCR does not predict a different outcome and indicate that more sensitive techniques are able to identify patients with differing prognoses. We suggest that MRD categories should be implemented over sCR for the future classification of MM responses.

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

“…Intense research into new agents for MM management has led to a wide range of possible drug combinations [ 173 ]. One of the goals at present, especially in the context of first relapse, is to obtain bone marrow and PET&MRD negativity, which are associated with better PFS and OS outcomes [ 174 ]. Another interesting positive aspect is the incorporation of immunotherapy, including CAR-T cells, as a new therapeutic approach to improve survival [ 175 ].…”

Prediction of Early Treatment Response in Multiple Myeloma Using MY-RADS Total Burden Score, ADC, and Fat Fraction From Whole-Body MRI: Impact of Anemia on Predictive Performance

“…The response category was recorded from the EMR. For purposes of this investigation, patients with sCR, CR, or VGPR were considered to have deep response (reflecting studies showing similar PFS among these patients [31,32]), while patients with PR, MR, or SD were considered to not have deep response.…”

Minimal Residual Disease in Multiple Myeloma: Potential for Blood-Based Methods to Monitor Disease

“…Stringent complete remission (sCR) is a deeper level of response assessment than CR, but recently the value of sCR remission has been questioned. A 2020 study involving 193 patients across two institutions determined that MRD should be implemented over sCR as it has a superior prognostic impact (13).…”