77relevance of ASCT in treatment of MM [ 33 ]. IMiDs and proteasome inhibitors are
the most frequently used agents for induction, consolidation and maintenance ther
apy ([ 21 , 34 – 39 ],) with substantial improvement in CR, OS and PFS rates.
Despite these promising results with the novel antimyeloma agents, HDchemotherapy
and ASCT is considered gold standard consolidative treatment in transplanteligible
myeloma patients. The novel antimyeloma agents have not replaced ASCT. In a recent
European phase III multicenter, randomized study, Gay et al. analyzed the clinical out
come of myeloma patients undergoing either HDC plus ASCT or conventional chemo
therapy plus lenalidomide (for consolidation treatment) followed by maintenance
therapy: after a median followup of 52 months the study showed that PFS was signifi
cantly higher with HDchemotherapy plus ASCT compared to chemotherapy plus
lenalidomide (43.3. vs. 28.6 months, p < 0.0001) [ 40 ]. Based on current prospective
data, the American Society for Blood and Marrow Transplantation (ASBMT) generally
recommends an early, upfront ASCT in newly diagnosed MM patients [ 10 ].
5.2.3 Single Versus Tandem ASCT
The role of two successive ASCT (tandem) visavis a single treatment is controver
sial in patients with multiple myeloma. Attal et al. published the first randomized
clinical trial analyzing the efficacy of single versus double ASCT in MM. All
together 399 newly diagnosed myeloma patients were enrolled in this study under
going induction therapy with VAD, single or tandem ASCT, and maintenance ther
apy with interferon (IFN). The 7year EFS was 10% in singletransplant group and
20% in tandemtransplant group (p = 0.03). The probability of surviving eventfree
for 7 years after the diagnosis was 10% in the singletransplant group and 20% in
the tandemtransplant group (P = 0.03). The estimated OS rate after 7 years was
21% in the singletransplant group and 42% in the doubletransplant group
(P = 0.01). Among patients who did not have a VGPR within three months after first
transplantation, the probability of surviving 7 years was 11% in the single transplant
and 43% in the transplanttransplant group (P < 0.001) [ 41 ]. In the Italian Bologna
96 clinical study (n = 321), upfront tandem ASCT was superior compared to single
ASCT regarding CR or near CR (47% vs. 33%, p = 0.008), relapsefree (42 vs.
24 months, p < 0.001) and EFS (35 vs. 23 months, p = 0.001) in newly diagnosed
MM patients [ 42 ].
Contradictory results were presented in two metaanalyses analyzing the role of
tandem ASCT in MM, revealing that no apparent improvement in EFS or OS was
noted by applying tandem ASCT [ 43 – 45 ]. Although not supported and administered
by other myeloma treatment centers, we believe that perspective tandem ASCT in
the setting of the Total Therapy approach (Fig. 5.2.) is an effective and potent treat
ment concept leading to cure in a large number of lowrisk MM patients [ 22 ].
5 Stem Cell Transplantation for Multiple Myeloma