A Multicenter Comparison of Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation with Tandem Autologous Stem Cell Transplantation in Multiple Myeloma.
Authors: Min Chang-Ki , Kim Hwak , Kim Kihyun , Kwak Jae-Yong , Lee Seung Tae , Won Jong Ho , Yoon Sung-Soo , Lee Jae Hoon , Suh Cheol Won 
Published: October 2019

Abstract
Background: Autologous stem-cell transplantation (ASCT) after high-dose chemotherapy is regarded as the standard therapeutic approach for multiple myeloma (MM) even if virtually all patients ultimately relapse following this procedure. Recently, tandem ASCT significantly improved overall survival (OS) and event-free survival (EFS) compared with single ASCT. Another strategy is to use reduced-intensity allogeneic stem cell transplantation (RISCT) earlier in the course of disease in chemosensitive patients. In the current study, we retrospectively analyzed the outcomes after a planned tandem ASCT or RISCT in the patients who previously underwent ASCT.
Patients and methods: One-hundred twenty-six patients who received a high dose (140 to 200 mg/m2) of melphalan as the conditioning regimen of the first ASCT were analyzed. Ninety-six patients (median age, 50.5 years) received a second ASCT, whereas 30 patients (median age, 46.5 years) underwent a RISCT (related in 28 patients and unrelated in 2 patients). The median interval between the first and second transplant was 131 days in tandem ASCT group and 157.5 days in RISCT group. The conditioning regimen for the tandem ASCT and RISCT consisted of high-dose melphalan ± total body irradiation (TBI) and fludarabine + melphalan or TBI, respectively. The two groups were evenly matched with regard to other disease characteristics.
Results: After a median follow-up of 664 days (range, 143–2904) from the first ASCT, the median event-free survival (EFS) and overall survival (OS) in all 126 patients were 878 days and 1838 days, respectively. The median EFS in the second ASCT vs. RISCT group were 844 days (95% CI, 714–973) and 1342 days (95% CI, 813–1870), respectively (P=0.262). The median OS in the tandem ASCT vs. RISCT group were 2160 days (95% CI, 1847–2832) and 1575 days (95% CI, 1202–1947), respectively (P=0.132). Disease-related mortality was not significantly different between the second ASCT vs. RISCT groups (73.3% vs. 60.0%, P=0.325) as well as treatment-related mortality between the 2 groups (26.7% vs. 40%, P=0.358). On multivariate analysis, an achieving a good response (≥ VGPR) after the induction treatment predicted a better EFS compared to a poor response (≤ PR) (RR; 0.245, P=0.01). A good response after first ASCT or the second transplant was associated with a better EFS by univariate analysis but not by multivariate analysis (RR; 0.927, P=0.830 or RR; 0.772, P=0.453, respectively).
Conclusion: In this retrospective analysis, ASCT followed by RISCT was not superior to the tandem ASCT, either EFS or OS. Disease-related deaths were not different between the 2 groups. Patients whose disease is sensitive to induction chemotherapy and who obtain a good response after the induction treatment benefited the most from this tandem transplant therapy.