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It is clear that MRD negative status can mean a longer Progression-Free Survival and/or Overall Survival for myeloma patients. My problem is, based on the second study linked below, I don’t see how an autologous stem cell transplant (Auto-HCT) improves things much for those patients reaching MRD status from induction therapy alone, given the cost of adverse events for those same MMers.
Full transparency- I believe that the less toxicity a MM sustains over the course of therapy, the better his/her life will be. MMers must balance the damage done by the myeloma with the damage done by toxic therapies. So when I read the stats from a study such as the Primer Study below, I try to figure out the benefit of high-dose therapy for MMers as well as the benefit of MRD negative status.
On a more technical note, the more chemo an MMer has the more likely that he/she will achieve multi-drug resistance aka MDR. My thinking is that based on the two articles linked below, MMers who achieve MRD after their induction therapy should not have an autologous stem cell transplant. Less can be more. If I read the chart correctly, MMers who achieve MRD during induction therapy can be as many as 43% of MMers.
Let me know if you have any questions.
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“MRD status can be used to evaluate patients’ response to therapy at all stages of treatment, he continues—prior to a stem cell transplant (to judge the effectiveness of pre-transplant chemotherapy); after transplant (to gauge the success of the transplant); and during and after maintenance therapy…”
“PRIMeR is the first U.S.-based ancillary study of MRD assessment by multiparameter flow cytometry (MFC).
Patients were enrolled on a national 3-arm RCT (BMT CTN 0702, STAMiNA trial, ClinicalTrials.gov Identifier: NCT01109004) comparing:
MRD was assessed at:
At a median follow-up of 38 months, there was no significant difference in PFS or OS by treatment arm in the subset of PRIMeR patients.
Univariate analysis demonstrated that being MRD negative at PM and Y1 was associated with better PFS, and at Y1, patients who were MRD negative also had longer OS (Table 1, Figures).
Multivariate analysis of time to progression or death, adjusting for disease risk, demonstrated hazard ratios (HR) in MRD negative patients compared to MRD positive patients at BL, PM and Y1 were 0.66 (p=0.07), 0.48 (0<0.001) and 0.22 (p<0.001) respectively.
Corresponding HRs for overall mortality were 0.81 (p=0.50), 0.77 (p=0.52) and 0.10 (0<0.001). The proportion of MRD negative patients at Y1 was highest (odds ratio 1.2) among patients randomized to the tandem AutoHCT arm (Table 2).
This is the first prospective U.S. cooperative group multi-center trial to demonstrate the prognostic value of MRD by MFC at PM and Y1 for PFS and OS with modern therapy including lenalidomide maintenance after AutoHCT.
MRD status is prognostic for PFS at all measured timepoints, and for OS at Y1. Despite better outcomes, patients with MRD negative MM at Y1 year still experienced disease progression (23% vs. 56% at 38 months after Auto HCT) despite continuous lenalidomide maintenance.
As MM is an incurable disease, MRD status may be a useful surrogate to direct further therapy which needs to be evaluated along with other clinical factors to predict long term PFS and OS. Additional analyses with longer follow-up are ongoing.