Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Lymphoma

Targeted based therapy in nodal T-cell lymphomas

Leukemia volume 35, pages 956–967 (2021)Cite this article

Subjects

Abstract

T-cell lymphomas (TCL) are a group of biologically and clinically heterogenous neoplasms derived from mature T lymphocytes. Recent findings in biology have advanced the classification of these neoplasms; however, clinical investigations based on biologic features have yet to be designed. Two biomarker-driven treatments for TCL are promising: brentuximab vedotin (BV) in combination with chemotherapy or as monotherapy is the standard treatment for newly diagnosed CD30-positive TCL and relapsed/refractory anaplastic large cell lymphoma (ALCL), while ALK inhibitors have induced responses in ALK+ ALCLs. Common genetic alterations in TCL, such as aberrations in PI3K/mTOR, JAK/STAT, and epigenetic regulators are also targetable by pathway inhibitors and HDAC/DNMT inhibitors; however, responses to these treatments as monotherapy are neither satisfactory nor durable, even in patients pre-stratified by several biomarkers. Additional work is needed to extend biology/biomarker-driven treatment in these neoplasms. As T-cell lymphomagenesis is multistep and multifactorial, trials are ongoing to evaluate combination treatments. The focus of this article is to summarize the status and the current role of targeted-based therapy in nodal TCL.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Current subtypes of nodal TCLs.

Similar content being viewed by others

References

  1. Adams SV, Newcomb PA, Shustov AR. Racial patterns of peripheral T-Cell lymphoma incidence and survival in the United States. J Clin Oncol. 2016;34:963–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chihara D, Ito H, Matsuda T, Shibata A, Katsumi A, Nakamura S, et al. Differences in incidence and trends of haematological malignancies in Japan and the United States. Br J Haematol. 2014;164:536–45.

    Article  PubMed  Google Scholar 

  3. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood. 2006;107:265–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA: a cancer J clinicians. 2016;66:443–59.

    Google Scholar 

  5. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Bellei M, Foss FM, Shustov AR, Horwitz SM, Marcheselli L, Kim WS, et al. The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project. Haematologica. 2018;103:1191–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chihara D, Fanale MA, Miranda RN, Noorani M, Westin JR, Nastoupil LJ, et al. The survival outcome of patients with relapsed/refractory peripheral T-cell lymphoma-not otherwise specified and angioimmunoblastic T-cell lymphoma. Br J Haematol. 2017;176:750–8.

    Article  CAS  PubMed  Google Scholar 

  9. Ellin F, Landstrom 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;124:1570–7.

    Article  CAS  PubMed  Google Scholar 

  10. Mak V, Hamm J, Chhanabhai M, Shenkier T, Klasa R, Sehn LH, et al. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors. J Clin Oncol. 2013;31:1970–6.

    Article  CAS  PubMed  Google Scholar 

  11. O’Connor OA, Pro B, Pinter-Brown L, Bartlett N, Popplewell L, Coiffier B, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30:631–6.

    Article  CAS  PubMed  Google Scholar 

  13. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, 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;30:2190–6.

    Article  CAS  PubMed  Google Scholar 

  14. O’Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, 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;33:2492–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Van Arnam JS, Lim MS, Elenitoba-Johnson KSJ. Novel insights into the pathogenesis of T-cell lymphomas. Blood. 2018;131:2320–30.

    Article  PubMed  Google Scholar 

  16. Jacobsen ED, Weinstock DM. Challenges and implications of genomics for T-cell lymphomas. Hematol Am Soc Hematol Educ Program. 2018;201:63–68.

    Article  Google Scholar 

  17. Sandell RF, Boddicker RL, Feldman AL. Genetic landscape and classification of peripheral T cell lymphomas. Curr Oncol Rep. 2017;19:28.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Heavican TB, Bouska A, Yu J, Lone W, Amador C, Gong Q, et al. Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma. Blood. 2019;133:1664–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang T, Feldman AL, Wada DA, Lu Y, Polk A, Briski R, et al. GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features. Blood. 2014;123:3007–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD, Weisenburger DD, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood. 2014;123:2915–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ma H, O’Connor OA, Marchi E. New directions in treating peripheral T-cell lymphomas (PTCL): leveraging epigenetic modifiers alone and in combination. Expert Rev Hematol. 2019;12:137–46.

    Article  PubMed  Google Scholar 

  22. Fukumoto K, Nguyen TB, Chiba S, Sakata-Yanagimoto M. Review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma. Cancer Sci. 2018;109:490–6.

    Article  CAS  PubMed  Google Scholar 

  23. Koch R, Christie AL, Crombie JL, Palmer AC, Plana D, Shigemori K, et al. Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas. Blood. 2019;133:566–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ng SY, Yoshida N, Christie AL, Ghandi M, Dharia NV, Dempster J, et al. Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models. Nat Commun. 2018;9:2024.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Weilemann A, Grau M, Erdmann T, Merkel O, Sobhiafshar U, Anagnostopoulos I, et al. Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma. Blood. 2015;125:124–32.

    Article  CAS  PubMed  Google Scholar 

  26. Boddicker RL, Kip NS, Xing X, Zeng Y, Yang ZZ, Lee JH, et al. The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-kappaB positive feedback loop in peripheral T-cell lymphoma. Blood. 2015;125:3118–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Buchan SL, Al-Shamkhani A. Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-kappaB signaling. PLoS One. 2012;7:e45244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sutherland MS, Sanderson RJ, Gordon KA, Andreyka J, Cerveny CG, Yu C, et al. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006;281:10540–7.

    Article  CAS  PubMed  Google Scholar 

  29. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017;130:2709–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chihara D, Fanale MA, Noorani M, Westin JR, Nastoupil L, Hagemeister FB, et al. The survival outcome of the patients with relapsed/refractory anaplastic large-cell lymphoma. Blood. 2015;126:2738.

    Article  Google Scholar 

  31. Chihara D, Wong S, Feldman T, Fanale MA, Sanchez L, Connors JM, et al. Outcome of patients with relapsed or refractory anaplastic large cell lymphoma who have failed brentuximab vedotin. Hematological Oncol. 2019;37:35–38.

    Article  CAS  Google Scholar 

  32. Bossard C, Dobay MP, Parrens M, Lamant L, Missiaglia E, Haioun C, et al. Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels. Blood. 2014;124:2983–6.

    Article  CAS  PubMed  Google Scholar 

  33. Sabattini E, Pizzi M, Tabanelli V, Baldin P, Sacchetti CS, Agostinelli C, et al. CD30 expression in peripheral T-cell lymphomas. Haematologica. 2013;98:e81–82.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Weisenburger DD, Savage KJ, Harris NL, Gascoyne RD, Jaffe ES, MacLennan KA, et al. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the international peripheral T-cell lymphoma project. Blood. 2011;117:3402–8.

    Article  CAS  PubMed  Google Scholar 

  35. Went P, Agostinelli C, Gallamini A, Piccaluga PP, Ascani S, Sabattini E, et al. Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol. 2006;24:2472–9.

    Article  CAS  PubMed  Google Scholar 

  36. Horwitz SM, Advani RH, Bartlett NL, Jacobsen ED, Sharman JP, O’Connor OA, et al. Objective responses in relapsed T-cell lymphomas with single agent brentuximab vedotin. Blood. 2014;123:3095–4100.

  37. Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, et al. Five-year outcomes for frontline brentuximab vedotin with CHP for CD30 expressing peripheral T-cell lymphomas. Blood. 2018;131:2120–4.

  38. Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, et al. Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. J Clin Oncol. 2014;32:3137–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Horwitz S, O’Connor OA, Pro B, Illidge T, Fanale M, Advani R, 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;393:229–40.

    Article  CAS  PubMed  Google Scholar 

  40. Voorhees T, Ghosh N, Dotti G, Savoldo B, Grover N, Beaven A. Long term remission in multiply relapsed enteropathy associated T-cell lymphoma type 1 following CD30 redirected chimeric antigen receptor T-cell therapy. La Jolla, CA: T-cell Lymphoma Forum; 2020.

  41. Hill LC, Rouce RH, Smith TS, Yang L, Srinivasan M, Zhang H, et al. Safety and anti-tumor activity of CD5 CAR T-cells in patients with relapsed/refractory T-cell malignancies. Blood. 2019;134:199.

    Article  Google Scholar 

  42. Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46:166–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, et al. Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses. J Hematol Oncol. 2014;7:11.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ghione P, Ozkaya N, Faruque P, Mehta-Shah N, Lunning MA, Ruan J, et al. Romidepsin activity in T follicular helper(TFH)-phenotype PTCL versus non TFH treated on the same clinical trials. J Clin Oncol. 2018;36:7509.

    Article  Google Scholar 

  45. Sawas A, Ma H, Shustov A, Hsu PL, Bhat G, Acosta M, et al. Belinostat induces high overall response rate (ORR) in patients with relapsed or refractory angioimmunoblastic T-cell lymphoma (AITL). Blood. 2019;134:4050.

    Article  Google Scholar 

  46. Lemonnier F, Dupuis J, Sujobert P, Tournillhac O, Cheminant M, Sarkozy C, et al. Treatment with 5-azacytidine induces a sustained response in patients with angioimmunoblastic T-cell lymphoma. Blood. 2018;132:2305–9.

    Article  CAS  PubMed  Google Scholar 

  47. Marchi E, Zullo KM, Amengual JE, Kalac M, Bongero D, McIntosh CM, et al. The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma. Br J Haematol. 2015;171:215–26.

    Article  CAS  PubMed  Google Scholar 

  48. O’Connor OA, Falchi L, Lue JK, Marchi E, Kinahan C, Sawas A, et al. Oral 5-azacytidine and romidepsin exhibit marked activity in patients with Ptcl: A Multicenter Phase I Study. Blood. 2019;134:1395–405.

  49. Falchi L, Ma H, Klein S, Lue JK, Montanari F, Marchi E, et al. Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: A Multicenter Phase 2 Study. Blood. 2020. Epub ahead of print.

  50. Ruan J, Moskowitz AJ, Mehta-Shah N, Sokol L, Chen Z, Rahim R, et al. Multi-center phase II study of oral azacitidine (CC-486) plus CHOP as initial treatment for peripheral T-cell lymphoma (PTCL). Blood. 2020;136:33–34.

    Article  Google Scholar 

  51. Johnston PB, Cashen AF, Nikolinakos PG, Beaven AW, Barta SK, Bhat G, et al. Safe and effective treatment of patients with peripheral T-cell lymphoma (PTCL) with the novel HDAC inhibitor, belinostat, in combination with CHOP: results of the Bel-CHOP phase 1 trial. Blood. 2015;126:253.

    Article  Google Scholar 

  52. Dupuis J, Morschhauser F, Ghesquieres H, Tilly H, Casasnovas O, Thieblemont C, et al. Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study. Lancet Haematol. 2015;2:e160–5.

    Article  PubMed  Google Scholar 

  53. Oki Y, Younes A, Copeland A, Hagemeister F, Fayad LE, McLaughlin P, et al. Phase I study of vorinostat in combination with standard CHOP in patients with newly diagnosed peripheral T-cell lymphoma. Br J Haematol. 2013;162:138–41.

    Article  CAS  PubMed  Google Scholar 

  54. Bachy E, Camus V, Thieblemont C, Casasnovas RO, Ysebaert L, Damaj GL, et al. Final analysis of the Ro-CHOP Phase III Study (Conducted by LYSA): romidepsin plus CHOP in patients with peripheral T-cell lymphoma. Blood. 2020;136:32–33.

    Article  Google Scholar 

  55. Enblad G, Hagberg H, Erlanson M, Lundin J, MacDonald AP, Repp R, 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;103:2920–4.

    Article  CAS  PubMed  Google Scholar 

  56. Wulf GG, Altmann B, Ziepert M, D’Amore F, Held G, Greil R, et al. Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial. Leukemia. 2020;35:143–55.

  57. Foss FM, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith MR, et al. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leuk Lymphoma. 2013;54:1373–9.

    Article  CAS  PubMed  Google Scholar 

  58. Foss F, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith M, et al. Denileukin diftitox (ONTAK) plus CHOP chemotherapy in patients with peripheral T-cell lymphomas (PTCL), the CONCEPT trial. Blood. 2007;110:3449.

    Article  Google Scholar 

  59. Collins GP, Horwitz SM, Davies A, Karnad A, Samaniego F, Spira AI, et al. Adct-301 (Camidanlumab Tesirine), a novel pyrrolobenzodiazepine-based CD25-targeting antibody drug conjugate, in a Phase 1 study of relapsed/refractory non-hodgkin lymphoma shows activity in T-cell lymphoma. Blood. 2018;132:1658.

    Article  Google Scholar 

  60. Marafioti T, Paterson JC, Ballabio E, Chott A, Natkunam Y, Rodriguez-Justo M, et al. The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation. Haematologica. 2010;95:432–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Chavez JC, Foss FM, William BM, Brammer JE, Smith SM, Prica A, et al. A phase I study of anti-ICOS antibody MEDI-570 for relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL) (NCI-9930). Blood. 2020;136:5–6.

    Article  Google Scholar 

  62. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263:1281–4.

    Article  CAS  PubMed  Google Scholar 

  63. Chihara D, Fanale MA, Miranda RN, Noorani M, Westin JR, Nastoupil LJ, et al. The risk of central nervous system relapses in patients with peripheral T-cell lymphoma. PLoS One. 2018;13:e0191461.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Bossi E, Aroldi A, Brioschi FA, Steidl C, Baretta S, Renso R, et al. Phase two study of crizotinib in patients with anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma relapsed/refractory to chemotherapy. Am J Hematol. 2020;12:E319–21.

  65. Nagai H, Fukano R, Sekimizu M, Kada A, Akiko MS, Asada R, et al. Phase II trial of CH5424802 (alectinib hydrochloride) for recurrent or refractory ALK-positive anaplastic large cell lymphoma: study protocol for a non-randomized non-controlled trial. Nagoya J Med Sci. 2017;79:407–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Gambacorti Passerini C, Farina F, Stasia A, Redaelli S, Ceccon M, Mologni L, et al. Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. J Natl Cancer Inst. 2014;106:djt378.

    Article  PubMed  Google Scholar 

  67. Mosse YP, Voss SD, Lim MS, Rolland D, Minard CG, Fox E, et al. Targeting ALK with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: A Children’s Oncology Group Study. J Clin Oncol. 2017;35:3215–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mosse YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14:472–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gambacorti-Passerini C, Mussolin L, Brugieres L. Abrupt relapse of ALK-positive lymphoma after discontinuation of crizotinib. N. Engl J Med. 2016;374:95–96.

    Article  PubMed  Google Scholar 

  70. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl J Med. 2013;368:2385–94.

    Article  CAS  PubMed  Google Scholar 

  71. Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017;355:1428–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fiore D, Cappelli LV, Broccoli A, Zinzani PL, Chan WC, Inghirami G. Peripheral T cell lymphomas: from the bench to the clinic. Nat Rev Cancer. 2020;20:323–42.

    Article  CAS  PubMed  Google Scholar 

  73. Luchtel RA, Dasari S, Oishi N, Pedersen MB, Hu G, Rech KL, et al. Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood. 2018;132:1386–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Horwitz SM, Koch R, Porcu P, Oki Y, Moskowitz A, Perez M, et al. Activity of the PI3K-delta,gamma inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood. 2018;131:888–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017;28:2169–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pro B, Brammer JE, Casulo C, Jacobsen E, Mead M, Mehta-Shah N, et al. Duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma from the phase 2 primo trial: dose optimization efficacy update and expansion phase initial results. Blood. 2020;136:38–39.

    Article  Google Scholar 

  77. Iyer SP, Haverkos BM, Zain J, Ramchandren R, Lechowicz MJ, Devata S, et al. Final results of phase 1/1b Study of Tenalisib, dual PI3K δ/γ inhibitor in patients with relapsed/refractory T-cell lymphoma. Blood. 2019;134:2831.

    Article  Google Scholar 

  78. Moskowitz AJ, Ghione P, Jacobsen ED, Ruan J, Schatz JH, Noor S, et al. Final results of a phase II biomarker-driven study of ruxolitinib in relapsed and refractory T-cell lymphoma. Blood. 2019;134:4019.

    Article  Google Scholar 

  79. Horwitz SM, Feldman TA, Hess BT, Khodadoust MS, Kim YH, Munoz J, et al. A phase 2 study of the dual SYK/JAK inhibitor cerdulatinib demonstrates good tolerability and clinical response in relapsed/refractory peripheral T-cell lymphoma and cutaneous T-cell lymphoma. Blood. 2019;134:466.

    Article  Google Scholar 

  80. Witzig TE, Reeder C, Han JJ, LaPlant B, Stenson M, Tun HW, et al. The mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma. Blood. 2015;126:328–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Witzig TE, Tang H, Micallef IN, Ansell SM, Link BK, Inwards DJ, et al. Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas. Blood. 2011;118:4882–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Witzig T, Sokol L, Jacobsen E, Advani AS, Mondejar R, Piris M, et al. Preliminary results from an open-label, phase II study of tipifarnib in relapsed or refractory peripheral T-cell lymphoma. Hematological Oncol. 2017;35:9–21.

    Google Scholar 

  83. Witzig TE, Sokol L, Foss FM, Kim WS, Jacobsen E, De La Cruz MDF, et al. Proof of concept for tipifarnib in relapsed or refractory angioimmunoblastic T-cell lymphoma (AITL) and CXCL12+ peripheral T-cell lymphoma (PTCL): preliminary results from an open-label, phase 2 study. Blood. 2019;134:468.

    Article  Google Scholar 

  84. Barta SK, Zain J, MacFarlane AWT, Smith SM, Ruan J, Fung HC, et al. Phase II study of the PD-1 inhibitor pembrolizumab for the treatment of relapsed or refractory mature T-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2019;19:356–64 e353.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Ratner L, Waldmann TA, Janakiram M, Brammer JE. Rapid progression of adult T-cell leukemia-lymphoma after PD-1 inhibitor therapy. N. Engl J Med. 2018;378:1947–8.

    Article  PubMed  Google Scholar 

  86. Rauch DA, Conlon KC, Janakiram M, Brammer JE, Harding JC, Ye BH, et al. Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade. Blood. 2019;134:1406–14.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Wartewig T, Kurgyis Z, Keppler S, Pechloff K, Hameister E, Ollinger R, et al. PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis. Nature. 2017;552:121–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Bennani NN, Pederson LD, Atherton P, Micallef I, Colgan JP, Thanarajasingam G, et al. A phase II study of nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma. Blood. 2019;134:467.

    Article  Google Scholar 

  89. Iyer SP, Xu J, Becnel MR, Nair R, Steiner R, Feng L, et al. A phase II study of pembrolizumab in combination with romidepsin demonstrates durable responses in relapsed or refractory T-cell lymphoma (TCL). Blood. 2020;136:40–41.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Fredrick B. Hagemeister for reviewing the manuscript.

Author information

Authors and Affiliations

  1. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Dai Chihara & Swaminathan P. Iyer

  2. Lymphoid Malignancy Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD, USA

    Milos Miljkovic

  3. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Francisco Vega

Authors
  1. Dai Chihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milos Miljkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Swaminathan P. Iyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco Vega
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dai Chihara.

Ethics declarations

Conflict of interest

SPI has research support from Rhizen, Seattle Genetics, Spectrum (Acrotech), Affimed, Trillium, CRISPR Therapeutics, Legend Biotech, Daiichi Sankyo, Amgen and Consultant for Daiichi Sankyo, Sanofi, Seattle Genetics and Legend Biotech and speaker for Target Oncology and Curio Science. FV has research support from CRISPR Therapeutics and from NCI (R01 CA222918).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chihara, D., Miljkovic, M., Iyer, S.P. et al. Targeted based therapy in nodal T-cell lymphomas. Leukemia 35, 956–967 (2021). https://doi.org/10.1038/s41375-021-01191-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-021-01191-8

This article is cited by

Search

Advanced search

Quick links