79randomized, openlabel, phase III NCRI Myeloma X Relapse trial similar findings
were noted, showing that myeloma patients who underwent salvage ASCT had a
significant longer median time to progression compared to patients who only
received a cyclophosphamide based salvage regimen [ 47 ]. Giralt et al. have recently
released a consensus expert guideline on behalf of the International Myeloma
Working Group (IMWG), and other blood and bone marrow societies (EBMT,
ASBMT), indicating that HDchemotherapy and ASCT should be defined as stan
dard salvage therapy for MM patients who have relapsed after the primary therapy
that did not include ASCT. In patients who had ASCT in primary therapy and
relapsed after 18 months, HDchemotherapy and ASCT should be considered as
appropriate therapy as well. According to the expert opinion, the conditioning regi
men for ASCT in relapsed MM and maintenance therapy after ASCT need to be
further investigated in clinical trials, including application of novel agents, such as
IMiDs, proteasome inhibitors, and monoclonal antibodies [ 48 ].
5.2.5 ASCT in Elderly Patients
For a long period of time it was required that MM patient had to be less than 65 years
old in order to apply HDchemotherapy and ASCT. As MM mainly affects elderly
patients, a large number of patients were not considered suitable for HDchemotherapy
and ASCT. However, age above 65 years is no longer an exclusion criterion for appli
cation of HDchemotherapy and ASCT in MM. According to IMWG, elderly MM
patients can be divided into frail, intermediate and fit patients, depending on age,
comorbidities, cognitive and physical performance status. In conventionally treated
elderly MM patients (without ASCT), the 3year OS was 84% in fit, 76% in intermedi
ate, and 57% in frail subsets [ 49 ]. In the last couple of years the utilization of ASCT
has markedly increased mainly in the elderly patient population. In a large European
study with over 53.000 MM patients who underwent first ASCT between 1991 and
2010 it was clear that application of ASCT has increased in all age groups. However
the highest increase was noted in patients above the age of 65: from 1991–1995 only
3% received ASCT while 15 years later, from 2006–2010, 18.8% underwent
ASCT. The median 2 and 5year postASCT survival has considerably increased in
elderly patients (≥70 years) to 80.2% and 49.7%, respectively [ 50 ]. The continued
usage of ASCT in elderly patient is being challenged with the arrival of novel agents
that provide excellent clinical outcome with adequate tolerability. In their randomized
study, Facon et al. demonstrated that melphalan plus prednisone and thalidomide
(MPT) was associated with significantly better OS than HDC with melphalan (100 mg/
m^2 ) in elderly patients, 51.6 vs. 38.3 months respectively (p = 0.027) [ 51 ].
HDchemotherapy with melphalan 200 mg/m^2 followed by ASCT is associated with
high mortality rate in elderly patients [ 52 ]. It has been shown that with 30% dose
reduction of the conditioning regimen, HDchemotherapy and ASCT can be safely
performed. HDmelphalan with only 140 mg/m^2 based ASCT is less toxic and appears
to be equally effective as melphalan 200 mg/m^2 in elderly patients [ 52 ]. Badros et al.
demonstrated that with dose reduction of the conditioning regimen even tandem ASCT
is possible in newly diagnosed and pretreated, elderly myeloma patients [ 52 ].
5 Stem Cell Transplantation for Multiple Myeloma