**Author details**

*Multiple Myeloma*

renal dysfunction.

**4.12 Minimal residual disease**

cytometry (sensitive to 104

important with time [72].

**4.13 Next-generation sequencing**

into routine staging systems [4, 29].

**4.14 Predictive models in NDMM**

negative NDMM patient.

106

**4.11 Diabetes**

are worse [69]. As cyclophosphamide is hepatically cleared, cyclophosphamide, bortezomib, and dexamethasone remains standard induction regimen in individuals with compromised renal function. Melphalan, which is cleared through spontaneous hydrolysis, is another renal-independent therapeutic option. Previous risk-stratification systems have not addressed this conundrum with

Comorbidities present in NDMM patients play a strong role in what therapies may be available [70]. Diabetes mellitus, owing to concomitant progressive renal dysfunction and peripheral neuropathy, may limit the use or dose of certain novel therapies. Both IMiDs and proteasome inhibitors may worsen peripheral neuropathy, potentially limiting the dose able to be given or as a class altogether depending on the severity of neuropathy. Diabetic nephropathy poses similar limitations.

In every NDMM patient, there are an average of 3 to 5 clones present. These clones undergo mutations at varying degrees throughout the treatment course, with progression of disease presenting expansion of resistant clones over time. As a result, multiple myeloma is not considered to be a curable disease, and so an evolving treatment aim has been for maximal disease burden reduction [71]. The ability to reduce disease burden beneath the threshold of detection, known as minimal residual disease (MRD), has been shown to be an important prognostic indicator for survival and long-term outcomes. MRD has traditionally been detected by flow

cells). An evolving consensus is that achieving MRD-negative status at the time

NGS when it comes to FISH (seq-FISH) has improved sensitivity and similar specifically relative to clinical FISH studies and appears to identify a higher number of high-risk NDMM patients. These studies are currently ongoing to incorporate

Multiple advances in long-term survival have been made over time, with the potential for cure by some models. Heterogeneity of prognostic factors in multiple myeloma makes accurate prognostication difficult on an individual level. As a result, the use of prediction matrix and prognostic tools have aided our ability to assess overall survival. Furthermore, owing to the selection bias present within clinical trials populations, survival estimates derived from clinical trials limit the applicability to all "Real World" patients. The CONNECT registry was created as a prognostic model for OS in an unselected community and academic setting [66]. Prognostic models should take into account myeloma biology, patient comorbidities and include performance status and mobility assessment [73]. Next Gen Sequencing will offer a more comprehensive approach to treatment and the goal of a MRD

of induction therapy should be the goal of therapy. Though not-yet involved in staging systems, MRD-focused treatment assessments are becoming increasingly

cells) and next generation sequencing (NGS) (sensitive

**18**

Howard R. Terebelo1,2\* and Leo Reap1,2

1 Ascension Providence Hospital, Department of Hematology and Oncology, Southfield, Michigan, USA

2 Michigan State University, East Lansing, Michigan, USA

\*Address all correspondence to: hiccup@comcast.net

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
