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Multiple myeloma gammopathies

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis

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Abstract

This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). 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 intention-to-treat population (n= 199). Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months median follow-up, 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 0.36–0.84). Median overall survival (OS) was 70.2 versus 71.8 months (P= 0.856). Two-year non-relapse mortality with auto/allo versus tandem autoSCT was 14.3% versus 4.1% (P= 0.008). In patients harboring both del13q and del17p, 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). Our findings suggest that auto/alloSCT significantly extends PFS versus tandem autoSCT in del13q MM, and indicate some survival benefit for first-line alloSCT in high-risk MM.

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Acknowledgements

We would like to thank the patients who consented to participate, their families and caregivers, and the study nurses in the DSMM centers. We are indebted to Martina Haase, Lisa Hubert, Annette Nobis, and Verena Pscheidl for their help in putting long-term follow-up data together, and to Sandralee Lewis, PhD, working on behalf of the Investigator Initiated Research Writing Group (an initiative from Ashfield Healthcare Communications, part of UDG Healthcare plc), for medical writing support (funded by Würzburg University Medical Center). The trial was sponsored by Würzburg University, Würzburg, Germany.

Investigators of the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom) are as follows:

O. Sezer30, B. Dörken30, C. Gerecke31, S. Fuhrmann31, W. D. Ludwig31, B. Hertenstein32, M. Bormann32, R. Meyer33, R. Naumann34, U. Platzbecker34, Ch. Röllig34, W. Rösler35, I. von Metzler36, H. Martin36, M. Engelhardt37, J. Finke37, L. Trümper38, W. Jung38, Ch. A. Schmidt39, G. Dölken39, H. H. Wolf40, L. Müller40, K. Ligeti40, N. Kröger41, G. Schilling41, H. Dürk42, D. Peest43, A. Ganser43, M. Pfreundschuh44, H. Sayer45, M. von Lilienfeld-Toal45, L. O. Mügge45, M. Bentz46, M. Gramatzki47, M. Brüggemann47, T. Fischer48, D. Wolleschak10, G. Hess49, M. Kropff50, J. Reusch50, C. Straka51, H. Ostermann52, D. Franke52, C. Peschel53, T. Dechow53, F. Bassermann53, M. Hentrich54, H. Wandt55, K. Schäfer-Eckart55, B. Metzner56, G. Maschmeyer57, E. Holler58, C. Hart58, A. Reichle58, M. Freund59, S. Böttcher59, C. Kahl59, H. G. Mergenthaler60, W. Aulitzky61, M. Kaufmann61, J. Greiner62, E. Heidemann62, L. Kanz63, H. Hebart63, P. Liebisch3, D. Bunjes3, C. Langer3, N. Frickhofen64, H. Einsele1, S. Knop1, S. Mielke1, R. C. Bargou1, M. Svaldi65

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CM, CS, HH, and HE conceived and designed the work that led to the submission. SK, ME, PL, EH, BM, DP, MK, CAS, DB, TF, OS, MH, HO, FB, GH, BH, MF, MK, H-HW, WJ, NF, SM, RCB, GM, MS, CHL, MG, HH, LK, and HE acquired data and played an important role in interpreting the results. SK, ME, CM, and HE drafted the manuscript. PL, EH, BM, DP, MK, DB, CS, TF, OS, MH, HO, FB, GH, BH, MF, MK, CAS, H-HW, WJ, NF, SM, RCB, GM, MS, CHL, MG, HH, and LK revised the manuscript. CM conducted all the reported statistical analyses. All the authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Hermann Einsele.

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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, Tübingen, Germany): Scientific chairman: LK. HE reports grants, personal fees, and other (advisory board) from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda. The other authors declare that they have no conflict of interest.

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Investigators of the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom) are listed at the end of the paper.

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Knop, S., Engelhardt, M., Liebisch, P. et al. Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis. Leukemia 33, 2710–2719 (2019). https://doi.org/10.1038/s41375-019-0537-2

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