Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma

Few clinical studies have reported results of measurable residual disease (MRD) assessments performed as part of routine practice. Herein we present our single-institution experience assessing MRD in 234 multiple myeloma (MM) patients (newly diagnosed [NDMM = 159] and relapsed [RRMM = 75]). We describe the impact of depth, duration, and direction of response on prognosis. MRD assessments were performed by next-generation sequencing of immunoglobulin genes with a sensitivity of 10(-6). Those achieving MRD negativity at 10(-6), as well as 10(-5), had superior median progression-free survival (PFS). In the NDMM cohort, 40% of the patients achieved MRD negativity at 10(-6) and 59% at 10(-5). Median PFS in the NDMM cohort was superior in those achieving MRD at 10(-5) vs,10(-5) (PFS: 87 months vs 32 months; P < .001). In the RRMM cohort, 36% achieved MRD negativity at 10(-6) and 47% at 10(-5). Median PFS was superior for the RRMM achieving MRD at 10(-5) vs,10(-5) (PFS: 42 months vs 17 months; P < .01). Serial MRD monitoring identified 3 categories of NDMM patients: (A) patients with >= 3 MRD 10(-6) negative samples, (B) patients with detectable but continuously declining clonal numbers, and (C) patients with stable or increasing clonal number (>= 1 log). PFS was superior in groups A and B vs C (median PFS not reached [NR], NR, 55 respectively; P < .001). This retrospective evaluation of MRD used as part of clinical care validates MRD as an important prognostic marker in NDMM and RRMM and supports its use as an endpoint in future clinical trials as well as for clinical decision making.