Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study

被引：22

作者：

Chiappella, Annalisa ^{[1
]}

Dodero, Anna ^{[1
]}

Evangelista, Andrea ^{[2
]}

Re, Alessandro ^{[3
]}

Orsucci, Lorella ^{[4
]}

Usai, Sara Veronica ^{[5
]}

Castellino, Claudia ^{[6
]}

Stefoni, Vittorio ^{[7
]}

Pinto, Antonio ^{[8
]}

Zanni, Manuela ^{[9
]}

Ciancia, Rosanna ^{[10
]}

Ghiggi, Chiara ^{[11
]}

Rossi, Francesca Gaia ^{[12
]}

Arcari, Annalisa ^{[13
]}

Ilariucci, Fiorella ^{[14
]}

Zilioli, Vittorio Ruggero ^{[15
]}

Flenghi, Leonardo ^{[16
]}

Celli, Melania ^{[17
]}

Volpetti, Stefano ^{[18
]}

Benedetti, Fabio ^{[19
]}

Ballerini, Filippo ^{[20
]}

Musuraca, Gerardo ^{[21
]}

Bruna, Riccardo ^{[22
]}

Patti, Caterina ^{[23
]}

Leonardi, Francesco ^{[24
]}

Arcaini, Luca ^{[25
,26
]}

Magagnoli, Massimo ^{[27
]}

Cavallo, Federica ^{[28
]}

Bermema, Anisa ^{[1
]}

Tucci, Alessandra ^{[3
]}

Boccomini, Carola ^{[4
]}

Ciccone, Giovannino ^{[2
]}

Carniti, Cristiana ^{[29
]}

Pileri, Stefano Aldo ^{[30
]}

Corradini, Paolo ^{[1
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Div Hematol & Stem Cell Transplantat, Milan, Italy

[2] Azienda Osped & Univ Citta Salute & Sci & CPO Pie, Unit Clin Epidemiol, Turin, Italy

[3] ASST Spedali Civili Brescia, Hematol Div, Brescia, Italy

[4] Azienda Osped & Univ Citta Salute & Sci, Div Hematol, Turin, Italy

[5] Osped Oncol Armando Businco, Hematol Unit, Cagliari, Italy

[6] Azienda Osped S Croce & Carle, Div Hematol, Cuneo, Italy

[7] Univ Bologna, Inst Hematol Seragnoli, Bologna, Italy

[8] IRCCS, Fdn G Pascale, Ist Nazl Tumori, Hematol Oncol & Stem Cell Transplantat Unit, Naples, Italy

[9] Azienda Osped Santi Antonio & Biagio & Cesare Arr, Div Hematol, Alessandria, Italy

[10] Ctr Riferimento Oncol Aviano CRO IRCCS, Hematol, Aviano, Italy

[11] IRCCS Osped Policlin San Martino, Unit Hematol & Cellular therapies, Genoa, Italy

[12] Fdn IRCCS Ca Granda, Div Hematol, OM Policlin, Milan, Italy

[13] Osped Guglielmo Saliceto, Hematol Unit, Piacenza, Italy

[14] IRCCS Reggio Emilia, Hematol, Azienda USL, Reggio Emilia, Italy

[15] ASST Grande Osped Metropolitano Niguarda, Div Hematol, Milan, Italy

[16] Azienda Osped Perugia, Hematol, Perugia, Italy

[17] Osped Infermi, Hematol, Rimini, Italy

[18] ASUFC, Presidio Osped Univ Santa Maria della Misericordi, Clin Hematol, Udine, Italy

[19] Azienda Osped Univ Verona, Hematol & Stem Cell Transplantat, Verona, Italy

[20] IRCCS Osped Policlin San Martino, Hematol, Genoa, Italy

[21] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amado, Hematol unit, Meldola, Italy

[22] Osped Maggiore La Carita, Div Hematol, Novara, Italy

[23] Azienda Villa Sofia Cervello, Div Onco Hematol, Palermo, Italy

[24] Azienda Osped Univ Parma, Hematol & CTMO, Parma, Italy

[25] Univ Pavia, Fdn IRCCS Policlin San Matteo, Dept Mol Med, Pavia, Italy

[26] Fdn IRCCS Policlin San Matteo, Div Hematol, Pavia, Italy

[27] IRCCS Humanitas Res Hosp, Humanitas Canc Ctr, Dept Oncol & Hematol, Rozzano, Italy

[28] Univ Torino, Dept Mol Biotechnol & Hlth Sci, Div Hematol, Azienda Osped & Univ Citta Salute & Sci, Turin, Italy

[29] Fdn IRCCS Ist Nazl Tumori, Div Hematol & Stem Cell Transplantat, Lab Hematol, Milan, Italy

[30] European Inst Oncol IRCCS, Div Haematopathol, Milan, Italy

来源：

LEUKEMIA | 2023年 / 37卷 / 02期

关键词：

LONG-TERM REMISSIONS; ALLOGENEIC TRANSPLANTATION; IMPACT;

D O I：

10.1038/s41375-022-01780-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18-65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0-56.7), and the 18-month overall survival was 73.1% (95%CI:61.6-81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.

引用

页码：433 / 440

页数：8

共 27 条

[1] Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy [J].

Abramson, J. S. ;

Feldman, T. ;

Kroll-Desrosiers, A. R. ;

Muffly, L. S. ;

Winer, E. ;

Flowers, C. R. ;

Lansigan, F. ;

Nabhan, C. ;

Nastoupil, L. J. ;

Nath, R. ;

Goy, A. ;

Castillo, J. J. ;

Jagadeesh, D. ;

Woda, B. ;

Rosen, S. T. ;

Smith, S. M. ;

Evens, A. M. .

ANNALS OF ONCOLOGY, 2014, 25 (11) :2211-2217

[2] Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA) [J].

Bachy, Emmanuel ;

Camus, Vincent ;

Thieblemont, Catherine ;

Sibon, David ;

Casasnovas, Rene-Olivier ;

Ysebaert, Loic ;

Damaj, Gandhi ;

Guidez, Stephanie ;

Pica, Gian Matteo ;

Kim, Won Seog ;

Lim, Soon Thye ;

Andre, Marc ;

Garcia-Sancho, Alejandro Martin ;

Penarrubia, Maria Jesus ;

Staber, Philipp B. ;

Trotman, Judith ;

Huettmann, Andreas ;

Stefoni, Vittorio ;

Re, Alessandro ;

Gaulard, Philippe ;

Delfau-Larue, Marie-Helene ;

de Leval, Laurence ;

Meignan, Michel ;

Li, Ju ;

Morschhauser, Franck ;

Delarue, Richard .

JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (03) :242-+

[3] Impact of etoposide and ASCT on survival among patients aged <65 years with stage II to IV PTCL: a population-based cohort study [J].

Brink, Mirian ;

Meeuwes, Frederik O. ;

van der Poel, Marjolein W. M. ;

Kersten, Marie Jose ;

Wondergem, Marielle ;

Mutsaers, Pim G. N. J. ;

Bohmer, Lara H. ;

Woei-A-Jin, F. J. Sherida H. ;

Visser, Otto ;

Oostvogels, Rimke ;

Jansen, Patty M. ;

Plattel, Wouter ;

Huls, Gerwin A. ;

Vermaat, Joost S. P. ;

Nijland, Marcel .

BLOOD, 2022, 140 (09) :1009-1019

[4] Design of Phase II cancer trials evaluating survival probabilities [J].

L Douglas Case ;

Timothy M Morgan .

BMC Medical Research Methodology, 3 (1) :1-12

[5] Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification [J].

Cheson, Bruce D. ;

Fisher, Richard I. ;

Barrington, Sally F. ;

Cavalli, Franco ;

Schwartz, Lawrence H. ;

Zucca, Emanuele ;

Lister, T. Andrew .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3059-+

[6] Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy [J].

Coiffier, Bertrand ;

Pro, Barbara ;

Prince, H. Miles ;

Foss, Francine ;

Sokol, Lubomir ;

Greenwood, Matthew ;

Caballero, Dolores ;

Borchmann, Peter ;

Morschhauser, Franck ;

Wilhelm, Martin ;

Pinter-Brown, Lauren ;

Padmanabhan, Swaminathan ;

Shustov, Andrei ;

Nichols, Jean ;

Carroll, Susan ;

Balser, John ;

Balser, Barbara ;

Horwitz, Steven .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (06) :631-636

[7] Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma [J].

Corradini, P. ;

Vitolo, U. ;

Rambaldi, A. ;

Miceli, R. ;

Patriarca, F. ;

Gallamini, A. ;

Olivieri, A. ;

Benedetti, F. ;

Todeschini, G. ;

Rossi, G. ;

Salvi, F. ;

Bruno, B. ;

Baldini, L. ;

Ferreri, A. ;

Patti, C. ;

Tarella, C. ;

Pileri, S. ;

Dodero, A. .

LEUKEMIA, 2014, 28 (09) :1885-1891

[8] Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells [J].

Corradini, P ;

Dodero, A ;

Zallio, F ;

Caracciolo, D ;

Casini, M ;

Bregni, M ;

Narni, F ;

Patriarca, F ;

Boccadoro, M ;

Benedetti, F ;

Rambaldi, A ;

Gianni, AM ;

Tarella, C .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (11) :2172-2176

[9] Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-01 [J].

d'Amore, Francesco ;

Relander, Thomas ;

Lauritzsen, Grete F. ;

Jantunen, Esa ;

Hagberg, Hans ;

Anderson, Harald ;

Holte, Harald ;

Osterborg, Anders ;

Merup, Mats ;

Brown, Peter ;

Kuittinen, Outi ;

Erlanson, Martin ;

Ostenstad, Bjorn ;

Fagerli, Unn-Merete ;

Gadeberg, Ole V. ;

Sundstrom, Christer ;

Delabie, Jan ;

Ralfkiaer, Elisabeth ;

Vornanen, Martine ;

Toldbod, Helle E. .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (25) :3093-3099

[10] Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect [J].

Dodero, A. ;

Spina, F. ;

Narni, F. ;

Patriarca, F. ;

Cavattoni, I. ;

Benedetti, F. ;

Ciceri, F. ;

Baronciani, D. ;

Scime, R. ;

Pogliani, E. ;

Rambaldi, A. ;

Bonifazi, F. ;

Dalto, S. ;

Bruno, B. ;

Corradini, P. .

LEUKEMIA, 2012, 26 (03) :520-526

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