NODAL AND EXTRANODAL PERIPHERAL T/NK-CELL NEOPLASMS–CURRENT ASPECTS

  • Ivan Z Petković Univerzitet u Nišu Medicinski fakultet Niš, Departman za onkologiju Klinika za onkologiju,Klinički Centar Niš, Srbija

Sažetak


Peripheral T/NK–cell lymphomas (PTCL) are rare, bizarre, and extremely diverse cancers. The disease is prone to relapse with a high level of chemorefractoriness leading to a poor outcome. Almost 70% of patients will experience relapse, with a median 5–year overall survival (OS) in approximately 30%. Upfront management of PTCL has been extrapolated from the treatment paradigm for aggressive B–NHL. However, universally accepted induction is rather palliative than curative. Regardless of the maximal reinforcement of upfront management, only event free survival has been influenced but not OS. All actual guidelines emphasize the importance of the autologous stem cell transplantation (auto–SCT) as a consolidation of first major response. The allogeneic SCT (allo–SCT) is not evidence–based part of upfront management. Nevertheless, its use is justified in the relapsed/refractory setting. Unfortunately, the vast majority of patients are not candidates for aggressive treatment modalities making the recommended paradigm as limited feasible. Regarding such a situation novel compounds are warranted. Although presented data indicate ominous prognosis in PTCL it is important to denote that there has been evidence–based improvement in the treatment paradigm by the introduction of L–Asparaginase, and target therapy for CD30+ PTCL. In this sense, a considerable number of new compounds entered early phase trials and gave promising results. All lights have been focused on upcoming results given the fact that at the moment we have no much to offer for the patients who have relapsed or primary refractory.

Biografija autora

Ivan Z Petković, Univerzitet u Nišu Medicinski fakultet Niš, Departman za onkologiju Klinika za onkologiju,Klinički Centar Niš, Srbija

Odsek za maligne hemopatije, melanom, sarkome mekih tkiva i tumore nepoznatog primarnog ishodišta Klinika za onkologiju Klinički Centar Niš

Doc.dr sc. med. specijalista interne medicine, subspecijalista onkolog i hematoonkolog

Reference

Vose J, Armitage J, Weisenburger D. International peripheral T–cell and natural killer cell/T–cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008; 26 (25):4124–30.

Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haemotopoietic and Lymphoid Tissues. 4th ed. Geneva, Switzerland: World Health Organization; 2008.

Swerdlow SH, Campo E, Peleri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127 (20): 2375-90.

d’Amore F, Gaulard P, Trümper L, et al. Peripheral T–cell lymphomas: ESMO clinical practice guidelines for diagnosis, treatment and follow–up. Ann Oncol 2015; 26 suppl 26: 108-115.

Horwitz SM, Ansell SM, Ai WZ, et al. NCCN Guidelines Insights: T–cell lymphomas. Version 2.2018. J Natl Compr Canc Netw 2018; 16 (2): 123-35.

Biggar RJ, Engels EA, Frish M, et al. Risk of T-cell lymphoma in persons with AIDS. J Acquir Immune Defic Syndr 2000; 26 (4): 371-6.

de Jong D, Vasmel WL, de Boer JP, et al. Anaplastic large-cell lymphoma in women with breast implants. JAMA 2008; 300 (17): 2030-5.

Gaulard P, de Leval L. Pathology of peripheral T-cell lymphomas: where do we stand? Semin Hematol 2014; 51 (1): 5-16.

Asano N, Suzuki R, Kagami Y, et al. Clinicopathologic and prognostic significance of cytotoxic molecule expression in nodal peripheral T-cell lymphoma, unspecified. Am J Surg Pathol 2005; 29 (10): 1284-93.

Swerdlow SH, Jaffe ES, Brousset P, et al; International Lymphoma Study Group. Cytotoxic T-cell and NK-cell lymphomas: current questions and controversies. Am J Surg Pathol 2014; 38(10):e60-e71.

Perry AM, Warnke RA, Hu Q, et al. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood 2013; 122(22):3599-606.

Petrella T, Maubec E, Cornillet-Lefebvre P, et al. Indolent CD8-positive lymphoid proliferation of the ear: a distinct primary cutaneous T-cell lymphoma? Am J Surg Pathol 2007; 31 (12): 1887-92.

Sun JC, Lanier LL. NK cell development, homeostasis and function: parallels with CD8 T cells. Nat Rev Immunol 2011;11 (10): 645-57.

Lanier LL, Testi R, Bindl J, Phillips JH. Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 1989; 169 (6): 2233-8.

Chan JK, Tsang WY, Ng CS. Clarification of CD3 immunoreactivity in nasal T/natural killer cell lymphomas: the neoplastic cells are often CD3 epsilon+. Blood 1996; 87 (2): 839-41.

Felgar RE, Macon WR, Kinney MC, et al. TIA–1 expression in lymphoid neoplasms. Identification of subsets with cytotoxic T lymphocyte or natural killer cell differentiation. Am J Pathol 1997; 150 (6): 1893-900.

de Leval L, Rickman DS, Thielen C, et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 2007; 109 (11): 4952-63.

Iqbal J, Weisenburger DD, Greiner TC, et al. Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. Blood 2010; 115 (5): 1026-36.

Cuadros M, Dave SS, Jaffe ES, et al. Identification of a proliferation signature related to survival in nodal peripheral T-cell lymphomas. J Clin Oncol 2007; 25(22): 3321-9.

Dupuis J, Emile JF, Mouniar N, et al. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d’Etude des Lymphomes de l’ Adulte (GELA) study. Blood 2006; 108 (13): 4163-9.

Went P, Agostinelli C, Gallamini A, et al. Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol 2006; 24 (16): 2472-9.

Iqbal J, Wright G, Wang C, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T‐cell lymphoma. Blood 2014; 123 (19): 2915‐23.

de Leval L, Gaulard P. Pathobiology and molecular profiling of peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program 2008; 2008: 272-9.

Rodriguez-Pinilla SM, Atienza L, Murillo C, et al. Peripheral T-cell lymphoma with follicular T-cell markers. Am J Surg Pathol 2008; 32 (12): 1787-99.

Dupuis J, Boye K, Martin N, et al. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells. Am J Surg Pathol 2006; 30 (4): 490-4.

Grogg KL, Morice WG, Macon WR. Spectrum of bone marrow findings in patients with angioimmunoblastic T-cell lymphoma. Br J Haematol 2007; 137 (5): 416-22.

Sakata‐Yanagimoto M, Enami T,Yoshida K, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma.Nat Genet 2014; 46 (2): 171-5.

Attygalle AD, Kyriakou C, Dupuis J, et al. Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: clinical correlation and insights into natural history and disease progression. Am J Surg Pathol 2007; 31 (7): 1077-88.

Bayle C, Charpentier A, Duchayne E, et al. Leukaemic presentation of small cell variant anaplastic large cell lymphoma: report of four cases. Br J Haematol 1999; 104 (4): 680-8.

Kinney MC, Collins RD, Greer JP, et al. A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma. Am J Surg Pathol 1993; 17 (9): 859-68.

Castellar ERP, Jaffe ES, Said JW, et al. ALK‐negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 2014; 124 (9): 1473‐80.

Clemens MW, Brody GS, Mahabir RC, Miranda RN. How to diagnose and treat breast implant-associated anaplastic large cell lymphoma. Plast Reconstr Surg 2018; 141 (4): 586e-99e.

Loch-Wilkinson A, Beath K, Knight R, et al. Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand. Plastic Reconstr Surg 2017; 140 (4): 645-54.

Kim B, Roth C, Young V, et al. Anaplastic Large Cell Lymphoma and Breast Implants. Plastic Reconst Surg 2011; 128 (3): 629-39.

Yamaguchi M, Oguchi M, Suzuki R. Extranodal NK/T–cell lymphoma: Updates in biology and management strategies. Best Pract Clin Haematol 2018; 3(3):315-21.

Park S, Ko YH. Epstein–Barr virus–associated T/ natural killer–cell lymphoproliferative disorders. J Dermatol 2014; 41(1):29-39.

Tan SY, Ooi AS, Ang MK, et al. Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma. Leukemia. 2011; 25 (3): 555-7.

Quintanilla‐Martinez, L. The 2016 updated WHO classification of lymphoid neoplasias. Hematol Oncol 2017; 35 (S1): 37-45.

Savage KJ, Harris NL, Vose JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood 2008; 111 (12): 5496-504.

Ferreri AJ, Govi S, Pileri SA. Hepatosplenic gamma-delta T-cell lymphoma. Crit Rev Oncol Hematol. 2012; 83 (2): 283-92.

Elin F, Landström J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T–cell lymphomas: a study from the Swedish Lymphoma Registry. Blood 2014; 124 (10): 1570-7.

Schmitz N, Trumper L, Ziepert M, et al. Treatment and prognosis of mature T–cell and NK–cell lymphoma: an analysis of patients with T–cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group S0350. Blood 2010; 116 (18): 3418-25.

Carson KR, Horwitz SM, Pinter-Brown LC, et al. A prospective cohort study of patients with peripheral T–cell lymphoma in the United States. Cancer 2017; 123: 1174-83.

d'Amore F, Relander T, Lauritzsen GF, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012; 30 (25): 3093-99.

Schmitz N, de Leval L. How I manage T–cell lymphoma, not otherwise specified and angioimmunoblastic T–cell lymphoma: current practice and a glimpse into the future.Br J Haematol 2016; 176 (6): 851-66.

Petković I. Current trends in the treatment of primary mediastinal large B-cell lymphoma – an overview. Contemp Oncol (Poznan) 2015; 19 (6):428-35.

Maeda Y, Nishimori H, Hiramatsu Y, et al Dose-adjusted EPOCH chemotherapy for untreated periheral T–cell lymphomas: Multicenter phase II trial of West–Jhog PTCL 0707. Haematologica 2017; 102 (12): 2097-103.

Abramson JS, Feldman T, Kroll-Desrosiers AR, et al. Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy. Ann Oncol 2014; 25 (11): 2211-7.

Zinzani PL, Magagnoli M, Bendandi M, et al. Therapy with gemcitabine in pretreated peripheral T–cell lymphoma patients. Ann Oncol 1998; 9 (12): 1351-3.

Mahadevan D, Unger JM, Spier CM, et al. Phase 2 trial of combined cisplatin, etoposide, gemcitabine, and methylprednisolone (PEGS) in peripheral T-cell non-Hodgkin lymphoma: Southwest Oncology Group Study S0350. Cancer 2013; 119: 371-9.

Li L, Duan W, Zhang L, et al. The efficacy and safety of gemcitabine, cisplatin, prednisone, thalidomide versus CHOP in patients with newly diagnosed peropheral T–cell lymphoma with analysis of biomarkers. Br J Haematol 2017; 178 (5): 772-80.

Horwitz S, O’Connor O, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 2019; 393 (10168): 229-40.

Advani RH, Ansell SM, Lechowicz MJ, et al. A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial. Br J Haematol 2016; 172(4): 535-44.

Kim SJ, Yoon DH, Kang HJ, et al. Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: A multicentre, single-arm, phase 2 trial. Eur J Cancer 2012; 48: 3223-31.

Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol 2012; 30(18): 2190-6.

Zinzani PL, Venturini F, Stefoni V, et al. Gemcitabine as single agent in pretreated T-cell patients: evaluation of the long-term outcome. Ann Oncol 2010; 21(4): 860-3.

Damaj G, Gressin R, Bouabdallah K, et al. Results from a prospective, ope-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphoma: the BENTLY trial. J Clin Oncol 2013; 31(1): 104-10.

Corradini P, Dodero A, Zallio F, et al. 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 Clin Oncol 2004; 22: 2172-6.

Kanakry JA, Kasamon YL, Gocke CD, et al. Outcomes of related donor HLA-identical or HLA haploidentical allogeneic blood or marrow transplantation for peripheral T cell lymphoma. Biol Blood Marrow Transplant 2013; 19: 602-6.

Kyriakou C, Canals C, Finke J, et al. Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: A retrospective study from the lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2009; 27: 3951-8.

Feyler S, Prince HM, Pearce R, et al. The role of high-dose therapy and stem cell rescue in the management of T-cell malignant lymphomas: A BSBMT and ABMTRR study. Bone Marrow Transplant 2007; 40: 443-50.

Kim WS, Song SY, Ahn YC, et al. CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/ T–cell lymphoma? Ann Oncol 2001; 12 (3): 349-52.

Kwong YL, Kim WS, Lim ST, et al. SMILE for natural killer/T–cell lymphoma: analysis of safety and efficacy from Asia Lymphoma Study Group. Blood 2012; 120 (15): 2973-80.

Jaccard A, Gachard N, Marin B, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patient with refractory or relapsing extranodal NK/T–cell lymphoma, a phase 2 study. Blood 2011; 117 (6): 1834-9.

Avila M, Aquilar H, Demichelis GR, et al. Effectiveness of L-asparaginase-based regimens compared to anthracycline-based regimens in newly diagnosed extranodal NK/T-cell lymphoma, nasal type: a single Mexican center experience. Blood Res 2018; 53 (3): 210-17.

Bu S, Yuan F, Wei X, et al. L-asparaginase-based regimen as a first-line treatment for newly diagnosed nasal type extranodal natural killer cell/T-cell lymphoma. Exp Ther Med 2016; 11 (6): 2437-45.

Yang L, Liu H, XuXH, et al. Retrospective study of modified SMILE chemotherapy for advanced-stage, relapsed, or refractory extranodal natural killer (NK)/T–cell lymphoma, nasal type. Med Oncol 2013; 30 (4): 720.

Yamaguchi M, Tobinai K, Oguchi M, et al. Concurrent chemoradiothreapy for localized nasal natural killer/T–cell lymphoma: an updated analysis of the Japan clinical oncology group study JCOG0211. J Clin Oncol 2012; 30 (32): 4044-6.

Kwong YL, Chan TSY, Tan D, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T–cell lymphoma failing L–asparaginase. Blood 2017; 129 (17): 2437-42.

Hari P, Raj RV, Olteanu H. Targeting CD38 in refractory extranodal natural killer cell-T-cell lymphoma. N Engl J Med 2016; 375 (15): 1501–2.

Kim HK, Moon SM, Moon JH, Park JE, Byeon S, Kim WS. Complete remission in CD30-positive refractory extranodal NK/T-cell lymphoma with brentuximab vedotin. Blood Res 2015; 50 (4): 254-6.

Poon LM, Kwong YL. Complete remission of refractory disseminated NK/T cell lymphoma with brentuximab vedotin and bendamustine. Ann Hematol 2016; 95 (5): 847-9.

Malamut G, Chandesris O, Verkarre V, et al. Enteropathy associated T cell lymphoma in celiac disease: A large retrospective study. Dig Liver Dis 2013; 45: 377-84.

Nijeboer, P, de Baaij, L. R., Visser, O. , et al. Treatment response in enteropathy associated T‐cell lymphoma; survival in a large multicenter cohort. Am J Hematol 2015; 90: 493-8.

Jantunen E, Boumendil A, Finel H, et al. Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by EBMT. Blood 2013; 121: 2529-32.

Gentille C, Qin Q, Barbieri A, et al. Use of PEG-asparaginase in monomorphic epitheliotropic intestinal T-cell lymphoma, a disease with diagnostic and therapeutic challenges. Ecancermedicalscience 2017; 11: 771.

Voss MH, Lunning MA, Maragulia JC, et al. Intensive induction chemotherapy followed by early high-dose therapy and hematopoietic stem cell transplantation results in improved outcome for patients with hepatosplenic T-cell lymphoma: a single institution experience. Clin Lymphoma Myeloma Leuk 2013;13 (1): 8-14.

O’Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: Results from the pivotal PROPEL study. J Clin Oncol 2011; 29: 1182–9.

Qi W, Spier C, Liu X, et al. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment. Leuk Res 2013; 37(4): 434-9.

Barr PM, Li H, Spier C, et al. Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108. J Clin Oncol 2015; 33(21): 2399-404.

Friedberg JW, Mahadevan D, Cebula E, et al. Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas. J Clin Oncol 2014; 32(1): 44-50.

Islam S, Vick E, Huber B, et al. Co-targeting aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in peripheral T-cell lymphoma: a novel therapeutic strategy. Oncotarget 2017; 8(59):100326-38.

Shustov A, Coiffier B, Horwitz S, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017; 58 (10): 2335-41.

O’ Connor OA, Falchi L, Lue JK, et al. Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase I study. Blood 2019; e pub ahead of print

O’ Connor OA, Horwitz S, Masszi T, et al. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol 2015; 33 (23): 2492-9.

Gambacorti Passerini C, Farina F, et al. Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. J Natl Cancer Inst 2014; 106(2): djt378.

Thanarajasingam G, Edell ES, Markovic SM. Complete Response of Anaplastic Lymphoma Kinase-Mutated Refractory Extranodal Natural Killer/T-Cell Lymphoma to Crizotinib. Mayo Clin Proc 2016; 91 (9): 1319-20.

Horwitz SM, Koch R, Porcu P, et al. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood 2018; 131 (8): 888-98.

Oki Y, Haverkos B, Zain JM, et al. Tenalisib, a dual PI3K δ/γ inhibitor: Safety and efficacy results from an on-going phase I/Ib study in relapsed/refractory T-cell lymphoma. J Clin Oncol 2018; 36.15 suppl 7510 ASCO Abstract

Delarue R, Dupuis J, Sujobert P, et al. Treatment with hypomethylating agent 5-azacytidine inducessustained response in angioimmunoblastic T cell lymphomas. Blood 2016; 128: 4164A.

Makita S, Maeshima AM, Maruyama D, et al. Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review. Onco Targets Ther 2018; 11: 2287-93.

Witzig T, Sokol L, Jacobsen E, et al. Preliminary Results From An Open-Label, Phase II Study Of Tipifarnib In Relapsed Or Refractory Peripheral T-Cell Lymphoma. Hematol Oncol 2017; 35(S2): 251-2.

Ogura M, Ishida T, Hatake K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol 2014; 32(11): 1157-63.

Enblad G, Hagberg H, Erlanson M, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood 2004; 103 (8): 2920-4.

Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol 2016; 34(23): 2698-704.

Amengual JE, Lichtenstein R, Rojas C et al. The pralatrexate-romidepsin doublet: A well tolerated and highly effective combination for patients with relapsed or refractory peripheral T-cell lymphoma. Blood 2016; 128: 1824A.

Mehta-Shah N, Lunning MA, Boruchov AM et al. A phase I/II trial of the combination of romidepsin and lenalidomide in patients with relapsed/ refractory lymphoma and myeloma: Activity in T-cell lymphoma. J Clin Oncol 2015; 33 (suppl 15): 8521A.

Holkova B, Yazbeck V, KmieciakMet al. A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. Leuk Lymphoma 2017; 58 (6): 1349-57.

Mehta-Shah N, Moskowitz AJ, Lunning M et al. A phase Ib/IIa trial of the combination of romidepsin, lenalidomide and carfilzomib in patients with relapsed/refractory lymphoma shows complete responses in relapsed and refractory T-cell lymphomas. Blood 2016; 128: 2991A.

Fanale MA, Hagemeister FB, Fayad L et al. A phase I trial of alisertib plus romidepsin for relapsed/refractory aggressive B- and T-cell lymphomas. Blood 2014; 124: 1744A.

Moskowitz AJ, Koch R, Mehta-Shah N et al. In vitro, in vivo, and parallel phase I evidence support the safety and activity of duvelisib, a PI3K- inhibitor in combination with romidepsin or bortezomib in relapsed/refractory T-cell lymphoma. Blood 2017; 130 (suppl 1): 819A.

Objavljeno
2025/12/22
Rubrika
Pregledni rad / Review article