Skip to main content

Advertisement

Log in

Treatment of Peripheral T-cell Lymphoma: Are We Data Driven or Driving the Data?

  • Lymphoma (LI Gordon, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Peripheral T-cell lymphomas (PTCL) are a group of uncommon and heterogeneous malignancies arising from a postthymic or mature T-lymphocyte. The treatment of PTCL remains a challenging endeavor. Compared with the more common aggressive B-cell lymphomas, more patients with PTCL will be refractory to initial therapy and those who achieve responses often will have shorter progression-free survival. Despite retrospective data that suggest that anthracycline-based multiagent chemotherapy regimens may not provide a benefit compared with nonanthracycline regimens, nonanthracycline-based regimens, with the notable exception of L-asparaginase regimens for extranodal NK/T-cell lymphoma, have been disappointing so far. Based on phase II evidence and subset analyses available, we believe that the addition of etoposide to standard regimens and consolidation of first remissions with autologous stem cell transplantation (autoSCT) provides the best outcome in patients with PTCL and currently use CHOEP followed by ASCT for eligible patients with the common PTCL subtype: PTCL-NOS, AITL, and ALK negative ALCL. For those with ALK-positive ALCL standard CHOP or CHOEP is appropriate with consideration of ASCT only for those with high-risk disease. Other strategies to incorporate additional agents, such as with dose-adjusted EPOCH or sequential CHOP-ICE regimens are logical options; however, they lack the supporting literature of CHOEP. Whereas the above recommendation is our current off-protocol approach, with the possible exception of low risk ALK positive ALCL, none of these choices is supported by strong enough data to supplant a well-conceived clinical trial as the truly preferred strategy in PTCL. The novel agents, romidepsin, pralatrexate, and brentuximab vedotin, are currently approved in the relapsed/refractory setting. These agents are being studied as additions or substitutions for other agents in up-front multiagent chemotherapy regimens. In the relapsed/refractory setting, both pralatrexate and romidepsin remain well-studied choices with some patients achieving a response with durability. Clinical trials of new agents in PTCL continue to be a valuable option and an important part of routine patient management as progressive disease often is seen. Lastly, we believe patients with relapsed/refractory PTCL should be considered for allogeneic stem cell transplantation if a suitable response is demonstrated and a willing donor is available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the international lymphoma study group. Blood. 1994;84(5):1361–92.

    PubMed  CAS  Google Scholar 

  2. 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(25):4124–30. The largest retrospective review on the prevalence and outcomes of PTCL and is broken down further by WHO subtypes. This article also reenforced the utility of the IPI as a prognostic index in PTCL as well as brought to question whether an antracycline based regimen is imparitive in the initial management of PTCL.

    Article  PubMed  Google Scholar 

  3. Savage KJ. Peripheral T-cell lymphomas. Blood Rev. 2007;21(4):201–16.

    Article  PubMed  CAS  Google Scholar 

  4. 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. 2012. doi:10.1016/j.clml.2012.09.002.

  5. Federico M, Rudiger T, Bellei M, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2012. doi:10.1200/JCO.2011.37.3647.

  6. Feldman AL, Sun DX, Law ME, et al. Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas. Leukemia. 2008;22(6):1139–43.

    Article  PubMed  CAS  Google Scholar 

  7. Wilcox RA, Sun DX, Novak A, Dogan A, Ansell SM, Feldman AL. Inhibition of Syk protein tyrosine kinase induces apoptosis and blocks proliferation in T-cell non-Hodgkin’s lymphoma cell lines. Leukemia. 2010;24(1):229–32.

    Article  PubMed  CAS  Google Scholar 

  8. Fitzgerald TJ, Neale GA, Raimondi SC, Goorha RM. c-tal, a helix-loop-helix protein, is juxtaposed to the T-cell receptor-beta chain gene by a reciprocal chromosomal translocation: t(1;7)(p32;q35). Blood. 1991;78(10):2686–95.

    PubMed  CAS  Google Scholar 

  9. Weisenburger DD, Savage KJ, Harris NL, 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(12):3402–8.

    Article  PubMed  CAS  Google Scholar 

  10. Feeney J, Horwitz S, Gonen M, Schoder H. Characterization of T-cell lymphomas by FDG PET/CT. AJR Am J Roentgenol. 2010;195(2):333–40.

    Article  PubMed  Google Scholar 

  11. Gascoyne RD, Aoun P, Wu D, et al. Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood. 1999;93(11):3913–21.

    PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood. 2004;103(7):2474–9.

    Article  PubMed  CAS  Google Scholar 

  14. Katsuya H, Yamanaka T, Ishitsuka K, et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol. 2012;30(14):1635–40.

    Article  PubMed  CAS  Google Scholar 

  15. Huang JJ, Zhu YJ, Xia Y, et al. A novel prognostic model for extranodal natural killer/T-cell lymphoma. Med Oncol. 2012;29(3):2183–90.

    Article  PubMed  CAS  Google Scholar 

  16. Xu PP, Wang Y, Shen Y, Wang L, Shen ZX, Zhao WL. Prognostic factors of Chinese patients with T/NK-cell lymphoma: a single institution study of 170 patients. Med Oncol. 2012;29(3):2176–82.

    Article  PubMed  CAS  Google Scholar 

  17. Zelenetz AD, Wierda WG, Abramson JS, et al. Non-Hodgkin’s lymphomas, version 3.2012. J Natl Compr Canc Netw. 2012;10(12):1487–98.

    PubMed  CAS  Google Scholar 

  18. Savage KJ, Chhanabhai M, Gascoyne RD, Connors JM. Characterization of peripheral T-cell lymphomas in a single north american institution by the WHO classification. Ann Oncol. 2004;15(10):1467–75.

    Article  PubMed  CAS  Google Scholar 

  19. 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. Blood. 2010;116(18):3418–25.

    Article  PubMed  CAS  Google Scholar 

  20. 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):3093–9. The largest study to date demonstrating the outcomes of autologous stecm cell transplant in first chemosensitive remisson in patients with the most common subtypes of PTCL (PTCL-NOS, AITL, and ALCL ALK negative). This study deferentiated induction regimens based on age (CHOEP vs CHOP). Patients with ALCL ALK negative did very well with this regimen. Mobilization following CHOEP did not appear to be an issue.

    Article  PubMed  Google Scholar 

  21. 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. 2012. doi:10.1002/cncr.27733. A prospective study utilizing a non-anthracycline based regimen in newly diagnosed and relapsed/refractory PTCL. The results demonstrated a low ORR (29 %) and a short PFS of 14 months in newly diagnosed patients.

  22. Ratner L, Harrington W, Feng X, et al. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One. 2009;4(2):e4420.

    Article  PubMed  Google Scholar 

  23. Tsukasaki K, Utsunomiya A, Fukuda H, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan clinical oncology group study JCOG9801. J Clin Oncol. 2007;25(34):5458–64.

    Article  PubMed  CAS  Google Scholar 

  24. Kluin-Nelemans HC, van Marwijk KM, Lugtenburg PJ, et al. Intensified alemtuzumab-CHOP therapy for peripheral T-cell lymphoma. Ann Oncol. 2011;22(7):1595–600.

    Article  PubMed  CAS  Google Scholar 

  25. d’Amore FLS, Gmes da Silva M et al. First interim efficacy and safety analysis of an international phase III randomized trial in newly diagnosed systemic peripheral T-cell lymphoma treated with chemotherapy with or without alemtuzumab and consolidated by high dose therapy. Blood (ASH Abstract #57). 2012.

  26. Ennishi D, Maeda Y, Fujii N, et al. Allogeneic hematopoietic stem cell transplantation for advanced extranodal natural killer/T-cell lymphoma, nasal type. Leuk Lymphoma. 2011;52(7):1255–61.

    Article  PubMed  Google Scholar 

  27. Ishida T, Hishizawa M, Kato K, et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. Blood. 2012;120(8):1734–41.

    Article  PubMed  CAS  Google Scholar 

  28. Itonaga H, Tsushima H, Taguchi J, et al. Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the nagasaki transplant group experience. Blood. 2013;121(1):219–25.

    Article  PubMed  CAS  Google Scholar 

  29. Falchook GS, Vega F, Dang NH, et al. Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment. Ann Oncol. 2009;20(6):1080–5.

    Article  PubMed  CAS  Google Scholar 

  30. Yamaguchi M, Kwong YL, Kim WS, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-cell tumor study group study. J Clin Oncol. 2011;29(33):4410–6. The first prospective study of a asparaginase based regimen (SMILE) in relapsed/refractory and newly diagnosed advanced stage NK/TCL patients. This study demonstrated a promising CR rate of 40 % in advanced stage patients. This regimen also demonstrated the ability to salvage patients with relapsed or refractory disease who had not seen asparaginase in the past highlighting the unique sensitivity of asparaginase in NK/TCL.

    Article  PubMed  CAS  Google Scholar 

  31. Li YX, Yao B, Jin J, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol. 2006;24(1):181–9.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  PubMed  CAS  Google Scholar 

  33. Phillips AA, Willim RD, Savage DG, et al. A multi-institutional experience of autologous stem cell transplantation in North American patients with human T-cell lymphotropic virus type-1 adult T-cell leukemia/lymphoma suggests ineffective salvage of relapsed patients. Leuk Lymphoma. 2009;50(6):1039–42.

    Article  PubMed  Google Scholar 

  34. Tsukasaki K, Maeda T, Arimura K, et al. Poor outcome of autologous stem cell transplantation for adult T cell leukemia/lymphoma: a case report and review of the literature. Bone Marrow Transplant. 1999;23(1):87–9.

    Article  PubMed  CAS  Google Scholar 

  35. Watanabe J, Kondo H, Hatake K. Autologous stem cell transplantations for recurrent adult T cell leukaemia/lymphoma using highly purified CD34+ cells derived from cryopreserved peripheral blood stem cells. Leuk Lymphoma. 2001;42(5):1115–7.

    Article  PubMed  CAS  Google Scholar 

  36. Fujiwara H, Arima N, Akasaki Y, et al. Interferon-alpha therapy following autologous peripheral blood stem cell transplantation for adult T cell leukemia/lymphoma. Acta Haematol. 2002;107(4):213–9.

    Article  PubMed  CAS  Google Scholar 

  37. O’Connor OA, Hamlin PA, Portlock C, et al. Pralatrexate, a novel class of antifol with high affinity for the reduced folate carrier-type 1, produces marked complete and durable remissions in a diversity of chemotherapy refractory cases of T-cell lymphoma. Br J Haematol. 2007;139(3):425–8.

    Article  PubMed  Google Scholar 

  38. O’Connor OA, Horwitz S, Hamlin P, et al. Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies. J Clin Oncol. 2009;27(26):4357–64.

    Article  PubMed  Google Scholar 

  39. Sandor V, Bakke S, Robey RW, et al. Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms. Clin Cancer Res. 2002;8(3):718–28.

    PubMed  CAS  Google Scholar 

  40. Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011;117(22):5827–34.

    Article  PubMed  CAS  Google Scholar 

  41. 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(9):1182–9. The seminal aritcle which led to the FDA approval of pralatrexate in relapsed/refractory PTCL. Of note, AITL as a distinct subtype had a lower ORR (8 %) to pralatrexate compared to PTCL-NOS and ALCL ALK negative.

    Article  PubMed  Google Scholar 

  42. Coiffier B, Pro B, Prince HM, 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(6):631–6.

    Article  PubMed  CAS  Google Scholar 

  43. Fanale MASA, Foereo-Torres A, Bartlett NL, Advani RJ, Pro B, et al. Brentuximab vedotin administered concurrently with multi-agent chemotherapy as frontline treatment of ALCL and other CD30-positive mature T-cell and NK-cell lymphoma. Blood (ASH Abstract #60). 2012.

  44. Rodriguez J, Munsell M, Yazji S, et al. Impact of high-dose chemotherapy on peripheral T-cell lymphomas. J Clin Oncol. 2001;19(17):3766–70.

    PubMed  CAS  Google Scholar 

  45. Rodriguez J, Caballero MD, Gutierrez A, et al. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol. 2003;14(12):1768–75.

    Article  PubMed  CAS  Google Scholar 

  46. Smith SD, Bolwell BJ, Rybicki LA, et al. Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen. Bone Marrow Transplant. 2007;40(3):239–43.

    Article  PubMed  CAS  Google Scholar 

  47. 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(11):2172–6.

    Article  PubMed  Google Scholar 

  48. Le Gouill S, Milpied N, Buzyn A, et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. J Clin Oncol. 2008;26(14):2264–71.

    Article  PubMed  Google Scholar 

  49. Jacobsen ED, Kim HT, Ho VT, et al. A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome. Ann Oncol. 2011;22(7):1608–13.

    Article  PubMed  CAS  Google Scholar 

  50. Goldberg JD, Chou JF, Horwitz S, et al. Long-term survival in patients with peripheral T-cell non-hodgkin lymphomas after allogeneic hematopoietic stem cell transplant. Leuk Lymphoma. 2012;53(6):1124–9.

    Article  PubMed  Google Scholar 

  51. Reimer P, Rudiger T, Geissinger E, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009;27(1):106–13.

    Article  PubMed  CAS  Google Scholar 

  52. Corradini P, Tarella C, Zallio F, et al. Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation. Leukemia. 2006;20(9):1533–8.

    Article  PubMed  CAS  Google Scholar 

  53. Mercadal S, Briones J, Xicoy B, et al. Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma. Ann Oncol. 2008;19(5):958–63.

    Article  PubMed  CAS  Google Scholar 

  54. Rodriguez J, Conde E, Gutierrez A, et al. Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from the gel-tamo study group. Eur J Haematol. 2007;79(1):32–8.

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

Matthew A. Lunning declares that he has no conflict of interest.

Steven Horwitz Consultancy for Allos, Seattle Genetics, BMS, Genzyme, Kyowa Hakko Kirin Pharma, Johnson & Johnson, Janssen, Millennium, and Celgene, and has grants/grants pending with Celgene, Allos, Seattle Genetics, Infinity Pharmaceuticals, Kyowa Hakko Kirin Pharma, and Millennium.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Steven Horwitz MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lunning, M.A., Horwitz, S. Treatment of Peripheral T-cell Lymphoma: Are We Data Driven or Driving the Data?. Curr. Treat. Options in Oncol. 14, 212–223 (2013). https://doi.org/10.1007/s11864-013-0232-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-013-0232-x

Keywords

Navigation