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Ferrata Storti Foundation
Plasma Cell Disorders
Long-term follow up of tandem autologous-allogeneic hematopoietic cell transplantation for multiple myeloma
Haematologica 2019 Volume 104(2):380-391
Damian J. Green,1,3 Marco Mielcarek,1,3 David G. Maloney,1,3* and Rainer Storb1,3*
Enrico Maffini,1 Barry E. Storer,1,2 Brenda M. Sandmaier,1,3 Benedetto Bruno,4 Firoozeh Sahebi,5 Judith A. Shizuru,6 Thomas R. Chauncey,1,3,7 Parameswaran Hari,8 Thoralf Lange,9 Michael A.Pulsipher,10
Peter A. McSweeney,11 Leona Holmberg,1,2 Pamela S. Becker,1,3
1Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA; 2University of Washington School of Public Health, Seattle, WA, USA and 3Department of Medicine, Seattle, WA, USA; 4University of Turin, Department of Molecular Biotechnology and Health Sciences, Turin, Italy; 5City of Hope National Medical Center/Southern California Kaiser Permanente Medical Group, Duarte, CA, USA; 6Stanford University, CA, USA; 7VA Puget Sound Medical Health Care System, Seattle, WA, USA; 8Medical College of Wisconsin, Milwaukee, USA; 9University of Leipzig, Germany; 10Children’s Hospital of Los Angeles, CA, USA and 11Colorado Blood Cancer Institute, Denver, CO, USA
*Co-senior authors.
ABSTRACT
We previously reported initial results in 102 multiple myeloma (MM) patients treated with sequential high-dose melphalan and autologous hematopoietic cell transplantation followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m2 and allogeneic hematopoietic cell transplantation. Here we present long- term clinical outcomes among the 102 initial patients and among 142 additional patients, with a median follow up of 8.3 (range 1.0-18.1) years. Donors included human leukocyte antigen identical siblings (n=179) and HLA-matched unrelated donors (n=65). A total of 209 patients (86%) received tandem autologous-allogeneic upfront, while thirty-five patients (14%) had failed a previous autologous hematopoiet- ic cell transplantation before the planned autologous-allogeneic trans- plantation. Thirty-one patients received maintenance treatment at a median of 86 days (range, 61-150) after allogeneic transplantation. Five- year rates of overall survival (OS) and progression-free survival (PFS) were 54% and 31%, respectively. Ten-year OS and PFS were 41% and 19%, respectively. Overall non-relapse mortality was 2% at 100 days and 14% at five years. Patients with induction-refractory disease and those with high-risk biological features experienced shorter OS and PFS. A total of 152 patients experienced disease relapse and 117 of those received salvage treatment. Eighty-three of the 117 patients achieved a clinical response, and for those, the median duration of survival after relapse was 7.8 years. Moreover, a subset of patients who became neg- ative for minimal residual disease (MRD) by flow cytometry experi- enced a significantly lower relapse rate as compared with MRD-positive patients (P=0.03). Our study showed that the graft-versus-myeloma effect after non-myeloablative allografting allowed long-term disease control in standard and high-risk patient subsets. Ultra-high-risk patients did not appear to benefit from tandem autologous/allogeneic hematopoietic cell transplantation because of early disease relapse. Incorporation of newer anti-MM agents into the initial induction treat- ments before tandem hematopoietic cell transplantation and during maintenance might improve outcomes of ultra-high-risk patients. Clinical trials included in this study are registered at: clinicaltrials.gov iden- tifiers: 00075478, 00005799, 01251575, 00078858, 00105001, 00027820, 00089011, 00003196, 00006251, 00793572, 00054353, 00014235, 00003954.
Correspondence:
rstorb@fredhutch.org
Received: June 21, 2018.
Accepted: September 24, 2018. Pre-published: September 27, 2018.
doi:10.3324/haematol.2018.200253
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/2/380
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