Second Autologous Stem Cell Transplantation Is Effective Salvage Therapy for Relapsed Multiple Myeloma.
Authors: Chaidos Aristeidis , Giles Chrissy , Auner Holger W , Bua Marco , Pavlu Jiri , Smith Ellena , Kanfer Edward , MacDonald Donald , Apperley Jane F. , Rahemtulla Amin 
Published: October 2019

Abstract
Abstract 1229
Poster Board I-251
Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is standard treatment for the non-elderly multiple myeloma (MM) patients. Relapses invariably occur and therefore reinduction therapy followed by ASCT is often considered. We retrospectively analysed the results of second ASCT after relapse and re-induction and assessed the effect of bortezomib therapy prior to second ASCT. We included 177 MM patients who relapsed after the initial melphalan 140-200mg/m2 ASCT and treated in a single institution from July 1994 to April 2009. Patients who received melphalan/TBI conditioning, planned upfront tandem transplants, allogeneic SCT, palliation only or who suffered early death or death in remission were excluded from our analysis. The patients were divided into 4 groups based on the type of salvage treatment. Group 1 included 96 patients with median age 59.6 years (range 31.16 – 73.5) at the time of progression who were salvaged with treatment modalities other than a second ASCT or bortezomib. Group 2 received bortezomib based salvage but not a second ASCT and included 31 patients aged 61.7 years (49.3 – 72.9), group 3 included 28 patients aged 58.6 years (31.1 – 70.6) who were treated with a second ASCT and no bortezomib, and finally group 4 included 22 patients aged 59.1 years (32.6 – 70.6) who were treated with bortezomib and second ASCT. For the transplanted patients, the conditioning consisted of melphalan 140-200mg/m2. Bortezomib was given at standard doses (1.3mg/m2 at days 1,4,8, and 11) plus dexamethasone 20mg same and next day of bortezomib injection for 3 to 4 21-day cycles. Survival was estimated from the time of progression after the initial transplant.
Univariate analysis showed longer survival for the transplanted patients (median 41.2 and 60.9 months for groups 3 and 4, 15.2 and 29.8 months for groups 1 and 2 respectively, Log Rank p=0.003). In multivariate Cox analysis the type of salvage treatment retained significance (p=0.013, OR 2.75, 95%CI 1.23 – 6.16). When patients treated with a second ASCT (groups 3 and 4) were analysed separately, the difference in survival between groups did not reach significance (p=0.32). Multivariate analysis showed longer survival if complete remission (CR) or near CR (nCR) had been achieved with the first ASCT (p=0.05, OR 6.4 95%CI 1.7 – 23.19) and if disease progression had occurred at least 12 months after the initial ASCT (p<0.001, OR 13 95%CI 3.74 – 45.15). The latter was also the only parameter to predict longer progression free survival (PFS) after the second ASCT (p=0.004, OR 5.2 95%CI 1.7 – 15.8). On the contrary, PFS was 19.1 months for group 3 and 10.1 months for group 4 (p=0.52). Similarly, age >65 years, reduced melphalan dose (<200mg/m2) and the immunoglobulin subtype of MM did not appear to affect the PFS or survival after a second ASCT. In conclusion, a second ASCT is an effective approach compared to other salvage treatments. A progression-free period of >12 months following the initial ASCT is the most significant prognostic factor of PFS and survival after the second ASCT. Bortezomib based induction is suggested to improve CR and nCR rates after the first ASCT, however its use prior to second ASCT does not appear to produce longer PFS or survival.

Disclosures
No relevant conflicts of interest to declare.