MRD Negativity is Better than Stringent Complete Response (sCR) to Determine Myeloma Patient Outcomes

In a head-to-head study comparing minimal residual disease (MRD) testing vs. using the "stringent complete response" measurement, MRD indicated a more accurate picture of long term outcomes for myeloma patients. Response criteria was developed ecades ago and is used in all myeloma clinical trials to assess efficacy of the treatments. Four categories of responses were defined by the International Myeloma Working Group. In 2006, a new "stringent complete response (sCR)" category was added to the criteria for patients who had the very best responses. 

More sensitive MRD testing is now available, so the study aim was to determine which classification was better - sCR or MRD? Based on the findings, the study authors suggested that: 

MRD categories should be implemented over sCR for the future classification of MM responses.

The study included 193 myeloma patients being treated at either the Hospital 12 Octubre in Madrid, Spain or the University of California at San Francisco (UCSF). The authors used either four-color flow cytometry (one cell in ten thousand or a hundred thousand cells) or next-generation sequencing (NGS) (one cell in a million cells) on the bone marrow biopsy samples to perform the MRD testing on samples received between 2003 and 2018. 

"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."

Patients who were MRD negative using flow cytometry (where the Progression Free survival had not yet been met) had better outcomes than those who did not reach MRD negativity (53 months). Similarly, patients who were MRD negative by NGS testing (such as Adaptive's ClonoSEQ test) also had superior outcomes (where the Progression Free survival had not yet been met) vs. patients who had not reach MRD negativity (38 months). 

“Our results confirm that response assessment according to the sCR criteria does not predict a different outcome for [patients with] MM with CR. However, more sensitive techniques, including both MFC and NGS of immunoglobulin genes, might identify patients with different prognoses, even among patients with sCR. These results confirm our previous findings and strengthen our suggestion that the sCR category should be rethought for the future classification of MM response,” the researchers concluded.

To learn more about the definitions of responses such as Stringent Complete Response, Complete Response, Very Good Partial Response, etc, click here.