-
1.
Autologous hematopoietic cell transplantation for relapsed multiple myeloma performed with cells procured after previous transplantation-study on behalf of CMWP of the EBMT
Drozd-Sokołowska, J., Gras, L., Zinger, N., Snowden, J. A., Arat, M., Basak, G., Pouli, A., Crawley, C., Wilson, K. M. O., Tilly, H., et al
Bone marrow transplantation. 2022
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.
PICO Summary
Population
Patients with multiple myeloma who relapsed after first autologous stem cell transplant (n=305)
Intervention
Stem cell remobilisation and autologous stem cell transplant (auto-HCT)
Comparison
None
Outcome
The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS.
-
2.
Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party
Hayden, P. J., Eikema, D. J., de Wreede, L. C., Koster, L., Kröger, N., Einsele, H., Minnema, M., Dominietto, A., Potter, M., Passweg, J., et al
Bone marrow transplantation. 2021
Abstract
The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p?0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p?=?0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P?=?0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p?0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
-
3.
Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT
Gagelmann, N., Eikema, D. J., de Wreede, L. C., Rambaldi, A., Iacobelli, S., Koster, L., Caillot, D., Blaise, D., Remémyi, P., Bulabois, C. E., et al
Bone marrow transplantation. 2020
-
-
-
Full text
-
Editor's Choice
Abstract
We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n?=?446), auto-auto (n?=?105), or auto-allo (n?=?72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p?=?0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p?=?0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p?=?0.007) and auto-allo (HR, 0.45; p?=?0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p?=?0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p?=?0.097). No significant difference in OS was identified between the groups in patients with del(17p).
PICO Summary
Population
Patients with newly diagnosed myeloma with del(17p) and/or t(4;14) (n=623)
Intervention
Autologous transplant (auto, n=446), tandem autologous (auto-auto, n=105)
Comparison
tandem autologous/reduced intensity allogeneic transplant (auto-allo, n=72)
Outcome
Five-year overall survival (OS) was 51% for single auto, 60% for auto-auto, and 67% for auto-allo Five-year progression-free survival (PFS) was 17%, 33%, and 34%. Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44) and auto-allo (HR, 0.45) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49;). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65).
-
4.
The Global State of Hematopoietic Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation (WBMT) Database and the Global Burden of Disease Study
Cowan, A. J., Baldomero, H., Atsuta, Y., Mikhael, J., Aljurf, M., Seber, A., Greinix, H., Koh, M., Worel, N., Libby, E. N., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
BACKGROUND Multiple myeloma (MM), is a plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. Access to effective therapy is limited globally. We report the rates and utilization of hematopoietic cell transplantation (HCT) globally from 2006-2015 to better characterize access to HCT for patients with MM. METHODS This was an analysis of a retrospective survey of Worldwide Network of Blood and Marrow Transplant sites, conducted annually between 2006-2015. Incidence estimates were from the Global Burden of Disease study. Outcome measures included total number of autologous and allogeneic HCTs by world regions, and percentage of newly diagnosed MM patients who underwent HCT, calculated by the number of transplants per region in calendar year / gross annual incidence of MM per region. RESULTS From 2006-2015, the number of autologous HCT performed worldwide for MM increased by 107%. Utilization of autologous HCT was highest in Northern America and European regions, increasing from 13% to 24% in Northern America, and an increase from 15% to 22% in Europe. In contrast, the utilization of autologous HCT was lower in the Africa/Mediterranean region, with utilization only changing from 1.8% in 2006 to 4% in 2015. The number of first allogeneic HCT performed globally for MM declined after a peak in 2012 by -3% since 2006. DISCUSSION Autologous HCT utilization for MM has increased worldwide in high-income regions but remains poorly utilized in Africa and the East Mediterranean. More work is needed to improve access to HCT for MM patients, especially in low to middle income countries.
-
5.
Tandem autologous stem cell transplantation improves outcome in newly diagnosed multiple myeloma with extramedullary disease and high-risk cytogenetics: a study from the Chronic Malignancies Working Party of EBMT
Gagelmann, N., Eikema, D. J., Koster, L., Caillot, D., Pioltelli, P., Lleonart, J. B., Remenyi, P., Blaise, D., Schaap, N., Trneny, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
-
-
-
Free full text
-
Editor's Choice
Abstract
Although high-dose therapy and autologous stem cell transplantation combined with novel agents is still the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease and high-risk cytogenetics is not defined yet. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with extramedullary disease undergoing single autologous (n=373), tandem autologous (n=84), or autologous-allogeneic transplantation (n=31) between 2003 and 2015. At least one high-risk abnormality was present in 41% (n=202), with del(17p) (40%) and t(4;14) (45%) being the most frequent. More than one high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival and progression-free survival of 54% and 29% vs. 78% and 49% for standard-risk (p<0.001, respectively). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, overall and progression-free survival were 70% and 43% for single autologous vs. 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic (p=0.06 and p=0.30). In multivariate analysis, high-risk cytogenetics were associated with worse survival (HR, 2.00; p=0.003) while tandem autologous significantly improved outcome vs. single autologous transplant (hazard ratios, 0.46 and 0.64; p=0.02 and p=0.03). Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival while results were limited due to small population (hazard ratio, 0.31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with extramedullary disease and significantly worsens outcome after single autologous while tandem autologous transplant strategy may overcome onset poor prognosis.
PICO Summary
Population
Adult myeloma patients with extramedullary disease (n=488).
Intervention
Tandem autologous transplantation (n=84) or autologous-allogeneic transplantation (n=31)
Comparison
Single autologous transplantation (n=373)
Outcome
Overall and progression-free survival were 70% and 43% for single autologous vs. 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic. In multivariate analysis, high-risk cytogenetics were associated with worse survival, while tandem autologous significantly improved outcome vs. single autologous transplant. Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival while results were limited due to small population.
-
6.
Conditioning-based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991-2012) on behalf of EBMT CMWP
Hayden, P. J., Iacobelli, S., Perez-Simon, J. A., van Biezen, A., Minnema, M., Niittyvuopio, R., Schonland, S., Meijer, E., Blaise, D., Milpied, N., et al
European journal of haematology. 2019
Abstract
OBJECTIVES The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma - Reduced Intensity Conditioning (RIC), Non-myeloablative, Myeloablative Conditioning (MAC), or Auto-Allo SCT - on outcomes in patients who had had a prior autologous transplant. METHODS A retrospective analysis of the EBMT database (1991-2012) was performed. RESULTS A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at five years were 39% (95%CI 31-47%), 45% (95%CI 32-57%), 19% (95%CI 6-32%), and 34% (95%CI 17-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P=0.004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR=4.1, p<0.001) but not after 2002 (HR=1.2, p=0.276). CONCLUSION From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.