Imaging in Stem Cell Transplant and Cell-based Therapy

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drugs for newly diagnosed and refractory/relapsing MM patients, such as protea­
some inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs
(IMiDs) (thalidomide, lenalidomide, pomalidomide), histone deacetylase (HDAC)
inhibitors (panobinostat) and most recently monoclonal antibodies (daratumumab,
elotuzumab) [ 7 , 8 , 11 – 19 ].
Kumar et  al. have demonstrated that the application of novel anti­myeloma
agents has significantly improved the OS rates in newly diagnosed (44.8 vs
29.9  months; p  <  0.001) and relapsed (23.9 versus 11.8  months; p  <  0.001) MM
patients [ 4 ]. Novel agents including proteasome inhibitors and IMiDs are routinely
used as part of the induction therapy before autologous transplantation which has
resulted in substantial improvement in the depth of response achieved before trans­
plant [ 20 ]. It is general practice to use a combination of a least three different drugs
for induction therapy prior to ASCT in order to achieve a high response and durable
complete remission (CR) rate [ 20 ]. In addition, the application of consolidation and
maintenance therapy in the post­ASCT setting is an increasingly attractive treat­
ment concept for patient with MM. Several studies demonstrate that consolidation
and maintenance post­ASCT can further reduce tumor burden and improve clinical
outcome [ 21 ].
Cure in MM is not anymore an unachievable goal [ 22 ]. A certain number of
myeloma patients, in particular low­risk myeloma patients, can achieve long­term
unmaintained, stringent­defined CR with OS rates of over more than 15 years [ 22 ].

5.2 HD-Chemotherapy and ASCT

5.2.1 Historic Background

In 1958, Blokhin et al. introduced melphalan as alkylating agent for treatment of six
patients with MM leading to considerable reduction in tumor size in half of the
patients [ 23 ]. In 1968 Alexanian et al. demonstrated that low­dose (LD) melphalan
(0.2 mg/kg/day or 0.7–1.3 mg/kg over 4 days, every 6 weeks) is effective in patient
with MM: from 82 myeloma patients 49% (n = 40) had an objective response rate
with improvement of clinical status and outcome [ 24 ]. The application of
LD­melphalan in combination with prednisone further improved OS in myeloma
patients compared to patient who only received LD­melphalan [ 25 ].
The experience with LD­melphalan has led to the introduction of dose­escalated
HD­melphalan in patients with MM in order to overcome drug resistance. In 1983
McElwain and Powles [ 26 ] administered HD­melphalan (100–140 mg/m^2 ) in eight
patients with MM and one patient with plasma cell leukemia. All of the patients
responded to the treatment and three out of the previously untreated patients (n = 5)
even achieved CR.  Despite these impressive results the clinical outcome was
impaired by the unacceptably high lethality rate of 20% and long aplasia phase with
neutropenia of 5–6 weeks [ 27 ]. The phase of aplasia was even 2–3 weeks longer in
myeloma patients who had prior treatment [ 27 , 28 ].

5 Stem Cell Transplantation for Multiple Myeloma