Page 39 - Haematologica Vol. 109 - July 2024

REVIEW ARTICLE - Minimal residual disease in multiple myeloma R. Szalat et al. Table 1. Available methods to assess bone marrow minimal residual disease in multiple myeloma.
BM: bone marrow; MRD: minimal residual disease; NGF: next-generation flow cytometry; NGS: next-generation sequencing.
Table 2. Available whole body imaging methods to complement bone marrow minimal residual disease assessment in multiple myeloma.
BM: bone marrow; CT: computed tomography; MM: multiple myeloma; PET: positron emission tomography; WBI: whole body imaging; wbMRI: whole body magnetic resonance imaging. *Useful to have WBI at diagnosis to evaluate response. Important to confirm if PET/CT positive at diagnosis.
BM-based MRD
NGF
NGS
BM evaluation
Yes
Yes
Standardization
Euroflow
Clonoseq
Evaluation required at diagnosis
Not required
Required
Fresh sample
Yes
No
Cost
+
++
Applicability
Universal
~90% of patients
Sensitivity
10^-5-10^-6
10^-6
WBI methods
PET/CT
wbMRI
BM evaluation
No
No
Standardization
Yes
Yes
Evaluation required at diagnosis
Not required* Negative in ~10% of MM patients
Not required*
Cost
++
++
Applicability
++
+
Sensitivity
++
+++
showing a high correlation (R2 = 0.905).74 As NGS and NGF are comparable, each method should be considered based on local availability. Complementary imaging methods to assess bone and EM MRD currently include wbMRI and PET/CT imaging, and provide additional information, while BM- and WB imaging-based methods have relative- ly good concordance and provide additional information, particularly regarding EMD and high-risk MM. WBI should, therefore, be used in combination with BM-based MRD in patients with high-risk or EM disease. Table 2 summarizes the characteristics of WB imaging methods. Some studies now support the benefit of combining both MRD methods in patient care.71
When should minimal residual disease assessment be performed?
Another important challenge regarding MRD utilization relates to its timeline. A first question is whether MRD evaluation should be done early during front-line treatment (for example, before SCT) or later on (after consolidation or during maintenance). Several trials have evaluated each of these time points, and because of the dynamic nature of MRD which implies transition from MRD positivity to negativity and vice-versa, it has become clear that several evaluations are, in fact, more informative. These observa- tions led to define the concept of ‘sustained’ MRD nega- tivity which appears to be the critical prognostic factor in MM.75 Having defined this concept led to another important
question, which is how much time should pass between the 2 time points. It seems that longer time points will likely be associated with better outcome, and studies are investigating if six months, one year or two years of MRD negativity are more relevant to potentially impact treatment decision. For example, in chronic myeloid leukemia (CML), strategies to stop therapy after two years of sustained MRD negativity have been developed.76,77 However, CML and MM are very different diseases biologically, and large phase III clinical trials are needed and are, indeed, ongoing to address this question. In future clinical practice, we anticipate that MRD assessment will be useful to evaluate the efficacy of a particular treatment strategy, before or after consolidation therapy or during maintenance in newly diagnosed myeloma and relapse/refractory disease. It is important to mention that the advent of cellular therapies including bi-specific antibodies and CAR T-cell therapy have revolutionized patient outcome and are associated with dynamic and often dissociated patterns of MRD and serological residual disease. Therefore, the role of MRD evaluation in the context of these novel therapies remains to be fully validated.78
How far is minimal residual disease evaluation useful in high-risk myeloma patients?
High-risk MM is defined by the presence of del17p, t(4;14), t(14;16), low albumin, high b2 microglobulin and elevated lactate dehydrogenase (LDH).79 MM patients experiencing
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