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6.1 Introduction
MM is a malignancy of terminally differentiated B cells characterized by a clonal
proliferation of plasma cells. The plasma cells accumulate in the bone marrow;
produce lytic bone lesions and excessive amounts of monoclonal proteins (usually
IgG or IgA type or free light chain) [ 1 ]. According to The American Cancer Society,
currently there are estimated 88,490 people living with myeloma in the United
States. Approximately 30,330 new cases will be diagnosed and about 12,650 deaths
are expected to occur in the year 2016 with this disease in US alone. MM is pre-
ceded by a premalignant stage called monoclonal gammopathy of undetermined
significance (MGUS) and asymptomatic smoldering MM. Rajkumar et al. have
elegantly summarized the diagnostic criteria of the International Myeloma Working
Group for premalignant and malignant MM [ 2 ]. The diagnosis is based on labora-
tory parameters in combination with bone marrow biopsy or bone marrow aspira-
tion which provide information about paraproteinaemia, plasma cell infiltration and
osteolytic bone destruction [ 3 ]. Approximately 80% patients present lytic bone
lesions with a high risk of pathological fractures, hypercalcaemia and bone pain.
Despite the major advancements in progression-free and overall survival with the
introduction of novel agents such as bortezomib and lenalidomide, the majority of
MM patients relapse, likely due to the outgrowth of refractory myeloma cells and
the disease remains essentially incurable [ 4 ]. Autologous stem cell transplantation
(ASCT) has been considered frontline therapy in newly diagnosed myeloma
patients; however, a range of combinations of novel drugs with ASCT, in a sequen-
tial treatment approach have recently become available, creating new opportunities
for clinical investigations [ 5 ]. The role of immunotherapy is increasingly recog-
nized in myeloma. A phenomenal number of immunostimulatory compounds, anti-
bodies, vaccines, for myeloma are in different stages of the development in either
animal model or clinical trials in conjunction with different agents. More recently,
two new monoclonal antibodies, daratumumab and elotuzumab, were approved by
the U.S. Food and Drug Administration (FDA) for myeloma. Furthermore, cellular
therapies such as dendritic cells, invariant natural killer T (iNKT) cells, natural
killer (NK) cells, chimeric antigen receptor-T (CAR-T) cells are also being evalu-
ated in different malignancies including myeloma. These therapies seem to have
great potential for long-term disease control and may be translated into the person-
alized cellular therapy [ 6 , 7 ].
One of the important challenges while dealing with tumors like multiple myeloma
is reliable real time assessment of tumor burden in response to different treatments.
Conventional radiography is a common technique that has been used in lab and
clinical setting for over 40 years for the real time assessment of tumor burden; how-
ever, it has several limitations [ 8 , 9 ]. Another commonly used approach to overcome
this challenge is luciferase transfection. This technique is used on the established
myeloma cell lines that are easy to transfect with luciferase and the tumor load is
assessed by live bio-imaging. However, primary myeloma cells, which are generally
available in limited numbers, survive poorly in vitro, and are extremely difficult
T.K. Garg and T. Pandey