Abstract

Multiple Myeloma (MM) is still an incurable disorder despite the numerous attempts to exploit new therapy approaches for it. The better understanding of its molecular pathogenesis has led to the development of effective, novel therapeutic agents like thalidomide and the proteasome inhibitor bortezomib. High-dose therapy with stem cell transplantation and novel targeted therapies represent two approaches to overcome resistance of multiple myeloma cells to conventional treatments. Autografting (AutoSCT) has been limited by high-relapse rates and conventional allografting (AlloSCT) by excessive TRM and toxicity. Reduced intensity conditioning for transplant (RICT), a less toxic procedure for AlloSCT that aims to exploit graft versus tumor effect, has been shown to achieve remissions in MM. High-dose therapy/AutoSCT followed shortly thereafter by RICT might improve outcomes in MM as compared to AutoSCT or conventional AlloSCT used alone. We compared two retrospective cohort of patients who underwent either tandem AutoSCT (HDT consisted of Melphalan 200 mg/m2) or AutoSCT followed closely by related RICT (patients with HLA-matched siblings). The two groups were matched for pre-transplant therapy, disease status at transplant, time from diagnosis to transplant. GVHD prophylaxis for RICT patients consisted of CyA/MTX. The major results are summarized in the Table. In the AutoSCT/RICT group the complete remission rate was higher (p=0.004) and the risk of disease progression after transplant was significantly reduced. All patients who reached CR responded after full chimerism and GVHD developed. This finding confirms the existence of a graft-versus-myeloma effect. Since the first clinical signs of response in remitters patients were noted between 70 and 120 days and maximum response between 160 and 200 days after RICT (after DLI in one patient), these responses should be considered immunological responses. Our data demonstrated that RICT following an AutoSCT can mediate a potentially curative graft-versus-myeloma effect and reduces the incidence of disease progression.

Tandem ASCT (N=35)ASCT+RICT (n=20)
Age, median 56 (range, 38–66) 51 (range, 34–63 
Median number of prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6) 
Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42) 
Conditioning Regimen for AutsoSCT Melphalan (200mg/m2) Melphalan (200mg/m2) 
Conditioning regimen for RICT --- TBI/Fludarabine 
Median days from AutoSCT to RICT --- 80 
Complete Remission rate 14% 50% 
Disease-free Survival at 4 yrs 14% 45% 
Overall Survival at 4 yrs 28% 40% 
Transplant-Related Mortality 0% 0% 
Tandem ASCT (N=35)ASCT+RICT (n=20)
Age, median 56 (range, 38–66) 51 (range, 34–63 
Median number of prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6) 
Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42) 
Conditioning Regimen for AutsoSCT Melphalan (200mg/m2) Melphalan (200mg/m2) 
Conditioning regimen for RICT --- TBI/Fludarabine 
Median days from AutoSCT to RICT --- 80 
Complete Remission rate 14% 50% 
Disease-free Survival at 4 yrs 14% 45% 
Overall Survival at 4 yrs 28% 40% 
Transplant-Related Mortality 0% 0% 

Disclosure: No relevant conflicts of interest to declare.

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