Title: Low-Dose Lenalidomide After Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation With Bortezomib as Graft-Versus-Host Disease Prophylaxis in High-Risk Multiple Myeloma
Abstract: Allogeneic (allo-) hematopoietic cell transplantation (HCT) with reduced-intensity conditioning remains an investigative approach for multiple myeloma as a result of the risks of nonrelapse mortality related to complications such as graft-versus-host-disease (GVHD). 1 Lokhorst H. Einsele H. Vesole D. et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol. 2010; 28: 4521-4530 Crossref PubMed Scopus (141) Google Scholar The addition of novel antimyeloma agents after HCT offers a potential means to reduce GVHD rates and maintain disease control. The administration of bortezomib after HCT has been shown to reduce the rate of acute GVHD in murine transplant models. 2 Sun K. Welniak L.A. Panoskaltsis-Mortari A. et al. Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Proc Natl Acad Sci U S A. 2004; 101: 8120-8125 Crossref PubMed Scopus (228) Google Scholar , 3 Sun K. Wilkins D.E. Anver M.R. et al. Differential effects of proteasome inhibition by bortezomib on murine acute graft-versus-host disease (GVHD): delayed administration of bortezomib results in increased GVHD-dependent gastrointestinal toxicity. Blood. 2005; 106: 3293-3299 Crossref PubMed Scopus (109) Google Scholar Moreover, bortezomib has been shown to be efficacious at maintaining myeloma control after allo-HCT without an increased risk of GVHD. 4 Kroger N. Zabelina T. Ayuk F. et al. Bortezomib after dose-reduced allogeneic stem cell transplantation for multiple myeloma to enhance or maintain remission status. Exp Hematol. 2006; 34: 770-775 Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar In the HOVON-76 trial, maintenance low-dose lenalidomide (10 mg daily for 21 days) provided 1 to 6 months after transplantation was found to be associated with a significant risk for acute GVHD. 5 Kneppers E. van der Holt B. Kersten M.J. et al. Lenalidomide maintenance after nonmyeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 trial. Blood. 2011; 118: 2413-2419 Crossref PubMed Scopus (147) Google Scholar Given the need for effective strategies to mitigate the deleterious effects of GVHD while reducing relapse risk, we conducted a phase 1 study to evaluate the safety of weekly bortezomib administered as GVHD prophylaxis and maintenance low-dose lenalidomide therapy among high-risk multiple myeloma patients receiving reduced-intensity conditioning allo-HCT.
Publication Year: 2019
Publication Date: 2019-07-01
Language: en
Type: letter
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 1
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