A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Schmitz, Norbert; Truemper, Lorenz; Bouabdallah, Krimo; Ziepert, Marita; Leclerc, Mathieu; Cartron, Guillaume; Jaccard, Arnaud; Reimer, Peter; Wagner-Drouet, Eva; Wilhelm, Martin; Sanhès, Laurence; Lamy, Thierry; Leval, Laurence de; Rosenwald, Andreas; Roussel, Murielle; Kroschinsky, Frank; Lindemann, Walter; Dreger, Peter; Viardot, Andreas; Milpied, Noël; Gisselbrecht, Christian; Wulf, Gerald; Gyan, Emmanuel; Gaulard, Philippe; Bay, Jacques‐Olivier; Glaß, Bertram; Poeschel, Viola; Damaj, Gandhi; Sibon, David; Delmer, Alain; Bilger, Karin; Banos, Anne; Haenel, Mathias; Dreyling, Martin; Metzner, Bernd; Keller, Ulrich; Braulke, Friederike; Friedrichs, Birte; Nickelsen, Maike; Altmann, Bettina; Tournilhac, Olivier

doi:10.1182/blood.2020008825

Cited by 56 publications

(64 citation statements)

References 27 publications

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“…In younger patients with T-cell lymphoma, standard chemotherapy consolidated by either autologous or allogeneic transplantation result in comparable survival, thus eliminating a role for allogenic stem cell transplantation in the first-line setting. 35 These results are in line with the retrospective analysis of the MD Anderson Cancer Center for patients with PTCLs that failed to show any difference in outcomes between ASCT and allogenic SCT. In addition, a CR prior to SCT initiation was associated with improved outcomes.…”

Section: Allogenic Stem Cell Transplantationsupporting

confidence: 82%

“…The role of allogenic SCT has been investigated recently by a randomized Phase 3 trial comparing ASCT and allogenic SCT as part of first-line therapy in poor-risk PTCL patients. 35 Patients received conventional chemotherapy with 4 cycles of CHOEP and 1 cycle of DHAP followed by intensification. Patients were randomized to receive BEAM followed by ASCT or myeloablative conditioning (fludarabine, busulfan, cyclophosphamide) followed by allogenic SCT from a matched related or unrelated donor.…”

Section: Allogenic Stem Cell Transplantationmentioning

confidence: 99%

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Updates in the Treatment of Peripheral T-Cell Lymphomas

Saleh¹,

Michot²,

Ribrag³

2021

JEP

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Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of rare hematologic malignancies accounting for less than 10% of non-Hodgkin lymphomas. The 2016 classification of World Health Organization recognized 29 different entities of PTCLs. These subgroups are characterized by different molecular and genetic patterns. For nearly 30 years, little improvement in the treatment of PTCLs has been noticed due to the paucity of randomized trials and anthracycline-based chemotherapy remains the mainstay of first-line treatment. In front-line setting, ECHELON-2, the first randomized controlled Phase III clinical trial, recently met its primary endpoint of PFS demonstrating the superiority of BV containing regimen when compared to standard CHOP in patients with CD30 positive PTCLs. The role of therapeutic intensifications such as autologous or allogenic stem cell transplantations remains controversial in first-line setting and in relapsed/refractory disease due to the lack of studies clearly addressing this question and the recently published negative studies. PTCLs are often refractory to first-line chemotherapy and tend to relapse after an initial response. New agents have been approved for relapsed/refractory disease such as Histone deacetylase inhibitors, folate analogue metabolic inhibitor or CD30 antibody drug conjugated. Despite an acceptable response to these agents, progression-free survival remains very poor. New strategies such as combinations of different agents have been evaluated in order to improve outcomes. Innovative drugs in the fields of epigenetics, immunomodulation within the tumor microenvironment, and direct targeting of tumor cells to CD30 and T-cell receptor abnormalities open new perspectives to improve the treatment of PTCLs.

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Section: Allogenic Stem Cell Transplantationsupporting

confidence: 82%

Section: Allogenic Stem Cell Transplantationmentioning

confidence: 99%

Updates in the Treatment of Peripheral T-Cell Lymphomas

Saleh¹,

Michot²,

Ribrag³

2021

JEP

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“…Patients in the 2 groups had similar survival rates, whereas patients with R/R-PTCL who underwent autologous HSCT had fewer AEs than who underwent allogeneic HSCT, likely because GVHD counterbalances the accompanying graft-vs-lymphoma effect after allogeneic HSCT. 40 However, considering the pretransplant status, most patients in the allogeneic HSCT group were insensitive to chemotherapy, and allogeneic HSCT served as a salvage therapy, which provided an additional survival advantage for patients with R/R-PTCL. These findings might be linked to the graft-vs-lymphoma effect.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma

Han

et al. 2021

JAMA Netw Open

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IMPORTANCE Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown.OBJECTIVE To compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL. DATA SOURCESA systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020. STUDY SELECTION After duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS], and transplantationrelated mortality [TRM]). Thirty trials were included in the meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.DATA EXTRACTION AND SYNTHESIS Data on study design, individual characteristics, and outcomes were extracted. All statistics were pooled by applying a random-effects model. MAIN OUTCOMES AND MEASURESThe prespecified main outcomes were OS, PFS, and TRM. RESULTSOf 6548 articles, data extracted from the 30 studies (including 880 patients who underwent allogeneic HSCT and 885 who underwent autologous HSCT) were included in this metaanalysis. In the allogeneic HSCT group, a 3-year OS of 50% (95% CI, 41%-60%) and PFS of 42% (95% CI, 35%-51%), a 5-year OS of 54% (95% CI, 47%-62%) and PFS of 48% (95% CI, 40%-56%), and a 3-year TRM of 32% (95% CI, 27%-37%) were observed. In the autologous HSCT group, a 3-year OS of 55% (95% CI, 48%-64%) and PFS of 41% (95% CI, 33%-51%), a 5-year OS of 53% (95% CI, 44%-64%) and PFS of 40% (95% CI, 24%-58%), and a 3-year TRM of 7% (95% CI, 2%-23%) were observed. CONCLUSIONS AND RELEVANCEIn this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.

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“…In fact, the value of this strategy has been addressed in a subsequent study by Park and coworkers [ 49 ], showing that whether ASCT in first complete remission (CR) could be of value in high-risk PTCL patients as a whole, it did not provide a significant PFS and OS advantage when the analysis was restricted in the specific PTCL_NOS subset. The role of first line allogeneic stem transplant (allo-SCT) consolidation has been evaluated in retrospective and prospective studies [ 43 , 50 ]. A recent phase 3 randomized study from Schmitz and coworkers [ 50 ] investigated the role of allo-SCT consolidation in first CR in PTCL.…”

Section: Prognosis and Therapymentioning

confidence: 99%

“…The role of first line allogeneic stem transplant (allo-SCT) consolidation has been evaluated in retrospective and prospective studies [ 43 , 50 ]. A recent phase 3 randomized study from Schmitz and coworkers [ 50 ] investigated the role of allo-SCT consolidation in first CR in PTCL. While confirming a strong graft versus lymphoma (GVL) effect and thus a lower relapse rate, this study did not demonstrate a significant OS advantage for allo-SCT, due to increased transplant related mortality (TRM) compared to ASCT.…”

Section: Prognosis and Therapymentioning

confidence: 99%

Peripheral T-Cell Lymphoma, Not Otherwise Specified: Clinical Manifestations, Diagnosis, and Future Treatment

Pileri

Tabanelli

Fiori

et al. 2021

Cancers

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Peripheral T-cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T-cell tumors, which overall represent 10–12% of all lymphoid malignancies. This category comprises all T-cell neoplasms, which do not correspond to any of the distinct entities listed in the WHO (World Health Organization) Classification of Tumours of Haematopoietic and Lymphoid Tissues. In spite of the extreme variability of morphologic features and phenotypic profiles, gene expression profiling (GEP) studies have shown a signature that is distinct from that of all remaining PTCLs. GEP has also allowed the identification of subtypes provided with prognostic relevance. Conversely to GEP, next-generation sequencing (NGS) has so far been applied to a limited number of cases, providing some hints to better understand the pathobiology of PTCL_NOS. Although several pieces of information have emerged from pathological studies, PTCL_NOS still remains a tumor with a dismal prognosis. The usage of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide) followed by autologous stem cell transplantation may represent the best option, by curing about 50% of the patients whom such an approach can be applied to. Many new drugs have been proposed without achieving the expected results. Thus, the optimal treatment of PTCL_NOS remains unidentified.

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A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Cited by 56 publications

References 27 publications

Updates in the Treatment of Peripheral T-Cell Lymphomas

Updates in the Treatment of Peripheral T-Cell Lymphomas

Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma

Peripheral T-Cell Lymphoma, Not Otherwise Specified: Clinical Manifestations, Diagnosis, and Future Treatment

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