Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Benefit from the Newer Drugs Used in the Relapsed Setting.
Authors: Hajek Roman , Krejci Marta , Scudla Vlastimil , Tothova Elena , Mistrik Martin , Bacovsky Jaroslav , Schutzova Miroslava , Koza Vladimir , Papajik Tomas , Novosadova Libuse , Frankova Hana , Stavarova Yvetta , Lehanka Frantisek , Vranova Milena , Kessler Petr , Zemanova Marketa , Meluzinova Ivana , Seifertova Nadezda , Sumna Elen , Pour Ludek , Maisnar Vladimir , Adam Zdenek 
Published: October 2019

Abstract
Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment of multiple myeloma (MM) patients (pts). In this report, we describe the longterm outcome of cohort of 185 pts with newly diagnosed symptomatic MM treated with ASCT. Median follow-up from the start of therapy was 102.8 months (range 67.2–150.4). We have specifically analyzed benefit from the newer drugs used in the relapsed setting.
Methods: A total of 185 MM pts underwent ASCT in the clinical trial 4W of Czech Myeloma Group in 18 centres in Czech Republic and Slovak Republic between 1996 and 2001. The conditioning regimen was high dose melphalan (200mg/m2) in all pts. At diagnosis of MM 72.4% (134/185) of pts had stage III according to Durie- Salmon, 18.4% (34/185) stage II and 9.2% (17/185) stage I. Clinical stages according to ISS were the following: stage 1 in 42.5% (74/174) of pts, stage 2 in 36.8% (64/174) and stage 3 in 20.7% (36/174) pts. Types of monoclonal immunoglobulin were as following: 67.6% (125/185) IgG, 21.1% (39/185) IgA, 9.7% (18/185) light chain, 1.6% (3/185) IgD. Renal insufficiency was presented in 5.9% (11/185) of pts. Median age at transplantation was 54.8 years (range: 28.3–69.2). When the symptomatic relapse of MM after ASCT was occurred, 34.6% (45/130) of pts were treated by conventional chemotherapy (CC) alone, 22.3% (29/130) by thalidomide based regimen, 10.7% (14/130) by bortezomib based regimen, 22.3% (29/130) pts underwent re-transplantation and 10% (13/130) of pts received combination of newer drugs and re-transplantation.
Results: Following ASCT, overall response rate (ORR) was 93.5% (173/185), 29.2% (54/185) of pts were in CR, 38.4% (71/185) of pts were in VGPR, 25.9% (48/185) of pts in PR. Median of overall survival (OS) from start of treatment was 77.9 months (9.6 – 147.3), median of TTP was 39.8 months (7.0–146.9). Total of 23.2% (43/185) of pts are alive and disease free, 20.5% (38/185) of pts are alive with relapse and 56.3% (104/185) of pts died with median follow-up 8.3 years from the start of therapy. Significant prognostic parameters for better OS after ASCT were: ISS stage < III (p<0.001), achievement of CR after ASCT (p<0.001) and the use of the newer drugs in the relapsed setting. Patients treated with thalidomide and/or bortezomib comparing to pts treated with CC only had significantly longer survival (p<0.001). Patients treated with re-transplantation only had not better OS (46.1 vs 37.8 months; p=0.224) comparing to pts treated with CC. In opposite, pts treated with the newer drugs and re-transplantation had better prognosis (OS 85.7 vs 37.8 months; p<0.001) than pts treated by CC. In multivariate analysis thalidomide and/or bortezomib treatment in the relapse was the strongest factor for long-term survival (beta 1.988; beta (exp) 7.303; CI: 2.860–18.645; p<0.001)
Conclusion: ASCT is effective procedure in MM pts. The achievements CR after transplantation, no presence of stage 3 according to ISS were significant parameters for long-term postransplant survival. Accessibility of the thalidomide and bortezomib was independent of other prognostic factors. The use of the newer drugs in the relapsed setting significantly improved prognosis of patients.