Long‐term outcome after allogeneic stem‐cell transplantation with reduced‐intensity conditioning in patients with multiple myeloma

This study examines the long‐term outcomes of a cohort of patients with myeloma who were treated with reduced‐intensity conditioning (RIC) regimens after a minimum follow‐up of 5 years at our centre. A total of 53 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem‐cell transplantation (Allo‐SCT) between January 2000 and January 2007 were identified. The median follow‐up of living patients was 84 months (51–141). The median age of the MM patients was 50 (28–70) years. Fifty‐one patients (96%) received a transplant from a sibling donor. The median time between diagnosis and Allo‐SCT was 34 months (6–161), and the median time between auto‐SCT and Allo‐SCT was 10 months (1–89). Fifty‐one patients (96%) received at least one auto‐SCT; 24 patients (45%) received a tandem auto‐Allo‐SCT. At last follow‐up, 21 patients (40%) are alive > 5 years post RIC Allo‐SCT. At last follow‐up, 14 (26%) are in first complete remission (CR), and four patients (8%) in second CR after donor lymphocyte infusion or re‐induction with one of the new anti‐myeloma drugs (bortezomib or lenalidomide) after Allo‐SCT. Eight patients (38%) among these long survivors received one of these new drugs as induction or relapse treatment before Allo‐SCT. Disease status and occurrence of cGvHD were significantly associated with progression‐free survival (PFS); hazard ratio (HR) = 0.62 (0.30–1.29, P = 0.20). Acute GvHD was correlated with higher transplant‐related mortality; HR = 4.19 (1.05–16.77, P = 0.04). No variables were associated with overall survival (OS). In conclusion, we observe that long‐term disease control can be expected in a subset of MM patients undergoing RIC Allo‐SCT. After 10 years, the OS and PFS were 32% and 24%, respectively. The PFS curve after Allo‐SCT stabilizes in time with a plateau after 6 years post Allo‐SCT. Am. J. Hematol. 88:370–374, 2013. © 2013 Wiley Periodicals, Inc.

[1]  KyungMann Kim,et al.  Contrasting treatment‐specific survival using double‐robust estimators , 2012 .

[2]  S. Giralt,et al.  Allogeneic hematopoietic stem cell transplantation for multiple myeloma: curative but not the standard of care , 2012, Current opinion in oncology.

[3]  D. Blaise,et al.  Lenalidomide plus donor-lymphocytes infusion after allogeneic stem-cell transplantation with reduced-intensity conditioning in patients with high-risk multiple myeloma. , 2012, Experimental hematology.

[4]  R. Storb,et al.  Allo-SCT for multiple myeloma: a review of outcomes at a single transplant center , 2012, Bone Marrow Transplantation.

[5]  R. Bouabdallah,et al.  Allogeneic transplant for myeloma in the era of new drugs: have the outcomes improved? , 2012, Leukemia & lymphoma.

[6]  A. Krishnan,et al.  Trends in allogeneic stem cell transplantation for multiple myeloma: a CIBMTR analysis. , 2011, Blood.

[7]  H. Goldschmidt,et al.  Treatment of relapsed and refractory multiple myeloma in the era of novel agents. , 2011, Cancer treatment reviews.

[8]  H. Einsele,et al.  International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  A. Zander,et al.  Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma , 2010, Cancer.

[10]  J. Bladé,et al.  Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. , 2010, Blood.

[11]  J. Bladé,et al.  Novel drugs for the treatment of multiple myeloma , 2010, Haematologica.

[12]  C. Hofmeister,et al.  Effects of induction with novel agents versus conventional chemotherapy on mobilization and autologous stem cell transplant outcomes in multiple myeloma , 2010, Leukemia & lymphoma.

[13]  N. Kröger,et al.  Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation , 2010, British journal of haematology.

[14]  M. Baccarani,et al.  Short-term thalidomide incorporated into double autologous stem-cell transplantation improves outcomes in comparison with double autotransplantation for multiple myeloma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  N. Kröger,et al.  Post-transplant immunotherapy with donor-lymphocyte infusion and novel agents to upgrade partial into complete and molecular remission in allografted patients with multiple myeloma. , 2009, Experimental hematology.

[16]  B. Barlogie,et al.  International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100) , 2009, Leukemia.

[17]  I. Yakoub-Agha,et al.  Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. , 2008, Blood.

[18]  J. Bladé,et al.  Prognostic factors for multiple myeloma in the era of novel agents. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[19]  H. Ljunggren,et al.  Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components. , 2008, Blood.

[20]  D. Blaise,et al.  High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after reduced intensity conditioning allogeneic stem cell transplantation for multiple myeloma , 2008, Haematologica.

[21]  R. Bouabdallah,et al.  Reduced-intensity conditioning allogeneic SCT as salvage treatment for relapsed multiple myeloma , 2008, Bone Marrow Transplantation.

[22]  G. Morgan,et al.  Peripheral blood or bone marrow cells in reduced-intensity or myeloablative conditioning allogeneic HLA identical sibling donor transplantation for multiple myeloma , 2007, Haematologica.

[23]  R. Bataille,et al.  Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. , 2007, Blood.

[24]  H. Goldschmidt,et al.  Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma. , 2006, Blood.

[25]  M. Qazilbash,et al.  Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma , 2006, Cancer.

[26]  H. Einsele,et al.  Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. , 2005, Blood.

[27]  R. Storb,et al.  Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. , 2003, Blood.

[28]  D. Blaise,et al.  Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. , 2003, Blood.

[29]  B. Barlogie,et al.  High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. , 2000, Blood.

[30]  G. Gahrton,et al.  Graft-versus-myeloma effect , 1996, The Lancet.

[31]  B. Barlogie,et al.  Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. , 1995, Blood.

[32]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[33]  J. Bladé,et al.  2010 Hematopoietic stem cell transplantation for multiple myeloma beyond , 2011 .

[34]  M. Dimopoulos,et al.  Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies , 2010, Leukemia.

[35]  R. Fanin,et al.  Bortezomib with or without dexamethasone in relapsed multiple myeloma following allogeneic hematopoietic cell transplantation. , 2006, Haematologica.