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1.
Durable benefit of rituximab maintenance post-autograft in patients with relapsed follicular lymphoma: 12-year follow-up of the EBMT lymphoma working party Lym1 trial
Pettengell, R., Uddin, R., Boumendil, A., Johnson, R., Metzner, B., Martín, A., Romejko-Jarosinska, J., Bence-Bruckler, I., Giri, P., Niemann, C. U., et al
Bone marrow transplantation. 2021
Abstract
We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P?=?0.002; HR 0.548 (95% CI 0.38-0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.
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2.
ASTCT, CIBMTR, and EBMT clinical practice recommendations for transplant and cellular therapies in mantle cell lymphoma
Munshi, P. N., Hamadani, M., Kumar, A., Dreger, P., Friedberg, J. W., Dreyling, M., Kahl, B., Jerkeman, M., Kharfan-Dabaja, M. A., Locke, F. L., et al
Bone marrow transplantation. 2021
Abstract
Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.
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3.
Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT
Kanate, A. S., Kumar, A., Dreger, P., Dreyling, M., Le Gouill, S., Corradini, P., Bredeson, C., Fenske, T. S., Smith, S. M., Sureda, A., et al
JAMA oncology. 2019
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Abstract
Importance: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma. Observations: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naive high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naive FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice. Conclusions and Relevance: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.
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Outcomes of advanced Hodgkin lymphoma after umbilical cord blood transplantation: a Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party study
Paviglianiti, A., Maio, K. T., Rocha, V., Gehlkopf, E., Milpied, N., Esquirol, A., Chevallier, P., Blaise, D., Gac, A. C., Leblond, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL) but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in EBMT centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 (47%) and almost all patients had received a previous autologous stem cell transplantation. The 4-year PFS and OS were 26% (95% CI 19-34%) and 46% (95% CI 37-55%), respectively. Relapse incidence was 44% (95% CI 36-54%) and non-relapse mortality (NRM) was 31% (95% CI 23-40%) at 4 years. In multivariate analysis, refractory/relapsed disease status at UCBT was associated with increased relapse incidence (HR=3.14 [95% CI 1.41-7.00], p=0.005) and NRM (HR=3.61 [95% CI 1.58-8.27], p=0.002), lower PFS (HR=3.45 [95% CI 1.95-6.10], p<0.001) and OS (HR=3.10 [95% CI 1.60-5.99], p=0.001). Conditioning regimen with cyclophospamide+fludarabine+2Gy total body irradiation (Cy+Flu+2 GyTBI) was associated with decreased risk of NRM (HR=0.26 [95% CI 0.10-0.64], p=0.004). Moreover, Cy+Flu+2 GyTBI conditioning regimen was associated with a better OS (HR=0.25 [95% CI 0.12-0.50], p<0.001) and PFS (HR=0.51 [95% CI 0.27-0.96], p=0.04). UCBT is feasible in heavily pretreated patients with HL. The reduced intensity conditioning regimen with Cy+flu+2 GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT.
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5.
High-dose therapy with BEAC conditioning compared to BEAM conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: no differences in toxicity or outcome. A matched-control study of the EBMT-Lymphoma Working Party
Robinson, S. P., Boumendil, A., Finel, H., Dreger, P., Sureda, A., Hermine, O., Montoto, S.
Bone marrow transplantation. 2018
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Editor's Choice
Abstract
A recent shortage of melphalan has prompted the use of alternatives to BEAM (BCNU, Etoposide, Cytarabine, Melphalan) conditioning for autologous stem cell transplantion (ASCT). The BEAC (BCNU, Etoposide, Cytarabine, Cyclophosphamide) regimen has been employed as a conditioning regimen in lymphoma patients. However, there have been recent concerns about the toxicity of BEAC. We conducted a retrospective analysis of the EBMT database comparing the outcome of patients conditioned using BEAC with a matched cohort of patients conditioned with BEAM. In the BEAC cohort (n = 383), 25 patients died from non-relapse mortality (NRM) events (32% owing to MOF or cardiac toxicity). In the BEAM cohort (n = 766) there were 34 NRM events (23% owing to MOF or cardiac toxicity). The 1-year cumulative incidence of NRM was 4% in the BEAC cohort and 3% in the BEAM group (p = ns). The 2-year relapse/progression rate was 32% with BEAC and 33% with BEAM (p = ns). At 2 years the progression-free survival (PFS) and overall survival (OS) were 63% and 78% for BEAC and 63% and 77% for BEAM-conditioned patients (p = ns for PFS and OS). The toxicity observed with BEAC conditioning as measured by NRM was similar to that seen with BEAM. The outcomes following BEAC were similar to those seen with BEAM, suggesting that BEAC is a safe conditioning regimen.
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Long-term outcome analysis of reduced-intensity allogeneic stem cell transplantation in patients with mantle cell lymphoma: a retrospective study from the EBMT Lymphoma Working Party
Robinson, S. P., Boumendil, A., Finel, H., Peggs, K. S., Chevallier, P., Sierra, J., Finke, J., Poiré, X., Maillard, N., Milpied, N., et al
Bone marrow transplantation. 2018;53(5):617-624
Abstract
Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and 5 years, respectively, and was associated with chemorefractory disease (HR 0.49, p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression-free survival rate and overall survival rate was 31 and 40%, respectively. RIST results in long-term disease-free survival in about 30% of the patients, including those patients relapsing after a prior autoSCT.
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Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party
Robinson, S. P., Boumendil, A., Finel, H., Blaise, D., Poire, X., Nicolas-Virelizier, E., Or, R., Malladi, R., Corby, A., Fornecker, L., et al
Bone Marrow Transplantation. 2016;51(3):365-71
Abstract
In the era of chemoimmunotherapy, the optimal treatment paradigm for relapsed and refractory diffuse large B-cell lymphoma has been challenged. We reviewed the outcome of standard salvage therapy with an autologous stem cell transplant (autoSCT) over the last two decades and the outcome of allogeneic SCT (alloSCT) in the most recent decade. AutoSCT recipients diagnosed between 1992 and 2002 (n=2737) were compared with those diagnosed between 2002 and 2010 (n=3980). Patients diagnosed after 2002 had a significantly lower non-relapse mortality (NRM) and relapse incidence (RI) and a superior PFS and overall survival (OS). A total of 4210 patients diagnosed between 2002 and 2010 underwent either an autoSCT or an alloSCT as their first transplant procedure. Two-hundred and thirty patients received an alloSCT (myeloablative (MACalloSCT) n=132, reduced intensity (RICalloSCT) n=98). The 4-year NRM rates were 7%, 20% and 27% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year RI was 45%, 40% and 38% for autoSCT, RICalloSCT and MACalloSCT, respectively (NS). The 4-year PFS were 48%, 52% and 35% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year OS was 60%, 52% and 38% for autoSCT, RIC alloSCT and MACalloSCT, respectively. After adjustment for confounding factors NRM was significantly worse for patients undergoing alloSCT whilst there was no difference in the RI.
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Reduced intensity allogeneic stem cell transplantation for follicular lymphoma relapsing after an autologous transplant achieves durable long term disease control. An analysis from the Lymphoma Working Party Of the EBMT
Robinson, S. P., Boumendil, A., Finel, H., Schouten, H., Ehninger, G., Maertens, J., Crawley, C., Rambaldi, A., Russell, N., Anders, W., et al
Annals of Oncology. , 2016 Mar 08. 2016
Abstract
BACKGROUND Patients with follicular lymphoma (FL) relapsing after an autologous transplant (autoSCT) may be treated with a variety of therapies including a reduced intensity allogeneic transplant (RICalloSCT). We conducted a retrospective analysis of a large cohort of patients undergoing RICalloSCT for FL in this setting. PATIENTS AND METHODS 183 patients, median age 45 years (range 21-69), had undergone an autoSCT at a median of 30 months prior to the RICalloSCT. Before the RICalloSCT they had received a median of 4 lines (range 3-10) of therapy and 81% of patients had chemosensitive disease and 16% had chemoresistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%). RESULTS With a median follow up of 59 months the non-relapse mortality (NRM) was 27% at 2 years. The median remission duration post autoSCT and RICalloSCT were 14 and 43 months respectively. The 5 year relapse/progression rate, progression free survival (PFS) and overall survival (OS) were 16%, 48% and 51% respectively and were associated with age and disease status at RICalloSCT. CONCLUSION This data suggests that a RICalloSCT is an effective salvage strategy in patients with FL recurring after a prior autoSCT and might overcome the poor prognostic impact of early relapse after autoSCT. Copyright © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.