Table 1.
Recommendations on Examinations at Diagnosis, Response Assessment, During Follow-up and at Relapse of MM.
| Tool | Diagnosis | At Response | At Follow-up | At Relapse | |
|---|---|---|---|---|---|
| Blood | Blood count and blood smear | Obligatory | Obligatory | Obligatory | Obligatory |
| Serum electrophoresis and IF | Obligatory | Obligatory (IF for CR confirmation) | Obligatory (IF for CR patients) | Obligatory | |
| Serum-free light chain | Obligatory | Obligatory to confirm sCR | Obligatory | Obligatory | |
| Serum immunoglobulin levels | Obligatory | Obligatory | Obligatory | Obligatory | |
| Renal and liver function tests | Obligatory | Obligatory | Obligatory | Obligatory | |
| Calcium | Obligatory | Obligatory | Obligatory | Obligatory | |
| Lactate dehydrogenase | Obligatory | Obligatory | Obligatory | Obligatory | |
| Albumin, β2m | Obligatory | Not required | Optional | Obligatory | |
| Flow cytometry | Optional | Not required | Not required | Optional | |
| Urine | Urine sample from 24 h urine collection to check for proteinuria and light-chain proteinuria | Obligatory | Obligatory | Obligatory | Obligatory |
| Urine electrophoresis and IF electrophoresis | Obligatory | Obligatory (IF for CR confirmation) | Obligatory (IF for CR patients) | Obligatory | |
| BM | BM cytology and biopsy to confirm plasmacytosis and monoclonality | Obligatory | Obligatory to confirm CR or for nonsecretory MM | Not required | Optional (obligatory for nonsecretory disease) |
| NGF or NGS to detect clonal plasma cells | Obligatory | Obligatory to confirm MRD negativity in CR or sCR patients | Every 12 mo in CR and/or MRD-negative patientsa | Optional | |
| Cytogenetics: karyotype and FISH for detection of del17p, t(4;14), t(14;16), ampl 1q/gain 1q, t(11;14) | Obligatory | Not required | Not required | Obligatory for del17p, ampl 1q/gain 1q and t(11;14) | |
| Advanced techniques: GEP, NGS | For clinical trials use only | For clinical trials use only | For clinical trials use only | For clinical trials use only | |
| Imaging | WBLD-CT | Obligatory | Not required | When symptomatic (or CT of the symptomatic area) | Obligatory |
| PET-CT | Optional (it may be carried out instead of WBLD-CT if available) | Obligatory to confirm imaging MRD | Every 12 mo in BM MRD-negative patientsb | Optional | |
| Whole-body MRI | Obligatory in WBLD-CT-negative cases and if PET-CT is not carried out | Not required | When symptomatic | Optional |
Adapted with permission from Caers et al.3
aSustained MRD negativity is supported by IMWG guidelines,4 although it is not fully reimbursed in several countries. In a recent “Real-World” study, MRD assessments were carried out in 139 patients before starting lenalidomide maintenance after ASCT and/or at the achievement of CR, while additional assessments were subsequently carried out on an annual basis until sustained MRD negativity was confirmed. In total, 34.3% of patients who were MRD-positive after induction treatment achieved MRD-negative status during maintenance and ultimately had improved PFS. Sequential MRD assessments identified patients with progressively decreasing MRD levels who also had better PFS outcomes, compared with patients not showing a decreasing pattern of MRD.5
bRecommended based on panel consensus in order to confirm extramedullary MRD negativity in patients who are MRD-negative in the BM.
ASCT = autologous stem cell transplantation; β2m = beta-2 microglobulin; BM = bone marrow; CR = complete response; CT = computed tomography; FISH = fluorescence in situ hybridization; GEP = gene expression profiling; IF = immunofixation; IMWG = International Myeloma Working Group; MM = multiple myeloma; MRD = minimal residual disease; MRI = magnetic resonance imaging; NGF = next-generation flow cytometry; NGS = next-generation sequencing; PET-CT = positron emission tomography-computed tomography; PFS = progression-free survival; sCR = stringent complete response; WBLD-CT = whole-body low-dose computed tomography.