Allogeneic Transplantation in Multiple Myeloma: Long-Term Follow-Up and Cytogenetic Subgroup Analysis

Background: Allogeneic (allo) following autologous (auto) stem-cell transplantation (SCT) has yielded conflicting results in newly diagnosed multiple myeloma (MM). In alloSCT, information is lacking regarding the impact of cytogenetic features except chromosome 13q deletion (del13q). Methods: This phase 3 trial compared tandem autoSCT versus autoSCT followed by reduced-intensity conditioning alloSCT (auto/alloSCT) in del13q MM. The availability/absence of a human leukocyte antigen-matched related or matched unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intent-to-treat population (n=199). Findings: Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months' median follow-up (range 2-143 months), median PFS with auto/allo versus tandem autoSCT was 34·5 versus 21.8 months (p=0·003; adjusted hazard ratio 0·55, 95% confidence interval [CI] 0·36-0·84). Median overall survival (OS) was 70.2 versus 71.8 months (p=0.856). Two-year non-relapse mortality (NRM) with auto/allo versus tandem autoSCT was 14·3% versus 4·1% (p=0·008). In patients harbouring both del13q and deletion of chromosome 17p, median PFS and OS were 37·5 and 61·5 months with auto/allo (n=19) versus 6·1 and 23·4 months with tandem autoSCT (n=6) (p=0·0002 and 0·032). Interpretation: Auto/alloSCT significantly extends PFS versus tandem autoSCT in patients with del13q MM. We believe this to be the first MM study demonstrating that MUD alloSCT can be performed with reasonable NRM. Furthermore, our data suggest some survival benefit for first-line alloSCT in high-risk MM. Funding: The trial was sponsored by Wurzburg University, Wurzburg, Germany. Declaration of Interest: MH reports personal fees from Amgen, Celgene, Janssen, Bristol-Myers Squibb, and Takeda. GH reports personal fees from Janssen, Roche, AbbVie, Gilead, Novartis, MorphoSys, and Celgene; and grants from Roche, Pfizer, and Celgene. SM reports non-financial support from EBMT/EHA, IACH, Celgene, Miltenyi, KIADIS, Bellicum, DGHO, Jazz Pharma, and ISCT; and personal fees from Celgene, Miltenyi, KIADIS, Bellicum, and Jazz Pharma. GM reports personal fees from Gilead, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, and Merck-Serono; and non-financial support from Janssen-Cilag. LK reports honoraria for presentation at “MedIpdate” (OnkoUpdate, IntemistenUpdate, PraxisUpdate) and at “Medizin Aktuell”. Amgen and Celgene are sponsors of the “Biannual International Stem Cell Conference, Tubingen, Germany): Scientific chairman: LK. HE reports grants, personal fees, and other (advisory board) from Janssen, Celgene, Amgen, BristolMyers Squibb, Novartis, and Takeda. All other authors declare no competing interests. Ethical Approval: The trial protocol was approved by the Wurzburg University ethics committee. All patients provided written informed consent prior to trial entry, and all procedures were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidelines for Good Clinical Practice.