Tandem Autologous(ASCT)/ Allogeneic Reduced Intensity Conditioning Transplantation (RIC) with Identical Sibling Donor Versus ASCT in Previously Untreated Multiple Myeloma (MM): Long Term Follow up of a Prospective Controlled Trial by the EBMT.
Authors: Gahrton Gosta , Bjorkstrand Bo , Iacobelli Simona , Hegenbart Ute , Gruber Astrid , Greinix Hildegard , Volin Liisa , Narni Franco , Musto Pellegrino , Beksac Meral , Bosi Alberto , Milone Giuseppe , Corradini Paolo , Goldschmidt Hartmut , de Witte Theo , Morris Curly , Niederwieser Dietger 
Published: October 2019

Abstract
Abstract 52

Introduction:
Allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning (RIC) is a controversial treatment in multiple myeloma. There are only few prospective studies and results are contradictory. The EBMT initiated a prospective study in the year 2000 comparing ASCT followed by RIC to ASCT. Patients and Method: 358 myeloma patients from 26 European centres were included in a prospective study comparing ASCT-RIC versus ASCT based on the availability of an HLA identical sibling donor. Patients with an HLA-identical sibling were allocated to the ASCT-RIC-arm (n=107) and patients without a matched sibling donor to the ASCT (n=251). Study inclusion was at the time of conditioning for the first autologous transplant at the achievement of a response status of at least stable disease after VAD ( vincristine, doxorubicine, dexamethasone)-like induction treatment of previously untreated patients. Single or tandem (n=122) autografting was optional in the ASCT arm. Conditioning for ASCT was melphalan 200 mg/m2, and for RIC fludarabine 30 mg/m2 × 3 plus TBI 2 Gy. The accrual period was from February 2001 to February 2005, and median follow-up time is 60 months. The two treatment groups were well matched for the standard prognostic parameters, karyotype (del(13) or not), and response status at ASCT. Results: On an intention to treat basis the cumulative 24 months non-relapse-mortality (NRM) was 13 % in the ASCT-RIC- and 5 % in the ASCT arm (p=0.014) and the CR rate was 43 % (CI:35-54%) and 38% (CI:32-45%) respectively. At 60 months after transplantation Relapse/Progression rate was 49% (CI: 40-60%) and 75% (CI: 69-80%) (significant at 5% level), PFS 35% (CI: 27-45%) and 18% (CI:14-24%) (significant at 5% level) and OS 65% (CI:56-74 %) and 57% (CI:51-64%) (at 84 months 60% and 22%) for the ASCT-RIC- and ASCT -arms, respectively. A comparison between those patients who received a second allo (n=88) versus a second auto (n= 104) the corresponding figures were for CR rate 51 % in the ASCT-RIC-arm and 43 % in the ASCT-arm, Relapse/Progession rate 45% and 77%, PFS 39% and 19% and OS 63% and 60% respectively. Information about the chromosome 13 deletion (del(13q14)) was present in 214 patients. In those with the deletion (n= 92) OS at 60 months was 70% and 53%, and PFS 30% and 11% for the ASCT-RIC- and ASCT-arms, respectively. The corresponding figures for patients without the deletion ( n=122) was for OS 70% vs 61% and PFS 44% vs 19%. Relapse rates were lower in the ASCT-RIC in both subgroups. Conclusion: The risk of myeloma relapse was significantly lower in the ASCT-RIC group as compared to ASCT group, both on an intention to treat analysis and when only those patients that received the correct treatment were analysed. NRM was significantly lower in the ASCT group, but still on an acceptable level in the ASCT-RIC group considering the significantly lower relapse/progression rate, improved PFS and a tendency for better long term OS. An improvement or tendency for improvement were seen in both poor (deletion 13) and good (no deletion 13) prognosis subgroups.

Disclosures:
Bjorkstrand: Roche: Employment, Karolinska Institutet employee until the closing of the study.