Hematopoietic Cell Transplantation and Adoptive Cell Therapy in Peripheral T Cell Lymphoma

Curr Hematol Malig Rep. 2020 Aug;15(4):316-332. doi: 10.1007/s11899-020-00590-5.

Abstract

Purpose of review: Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of diseases and represent approximately 10-15% of all non-Hodgkin lymphomas. Multiagent chemotherapy with a CHOP (cyclophosphamide, adriamycin, vincristine, prednisone)-like regimen is the current standard of care in the frontline setting, but outcomes for PTCL patients generally remain poor. Strategies used to improve survival and reduce the risk of relapse in PTCL patients include autologous hematopoietic cell transplant (autoHCT) and allogeneic HCT (alloHCT). Due to the relative rarity of these diseases, the evidence supporting the use of autoHCT and alloHCT is based on retrospective and single-arm prospective studies. Novel targeted therapies are now being incorporated into the treatment of PTCL, and they may play important roles in improving upon current standards of care. Herein, we summarize the evidence supporting HCT for the treatment of the most common PTCL histologic subtypes and highlight novel treatment strategies aimed at improving outcomes for these patients, including cutting-edge approaches using chimeric antigen receptor T cells (CAR-T).

Recent findings: Given recent improvements in OS and PFS in CD30+ PTCL using the drug-antibody conjugate brentuximab vedotin (BV), new questions arise regarding the impact of BV on consolidative autoHCT, and its role as a maintenance therapy. Multiple histone deacetylase inhibitors (HDACis) have been approved for the treatment of relapsed/refractory PTCL, and these agents are being incorporated into HCT approaches, both in the frontline and maintenance settings. Early data incorporating these agents into novel conditioning regimens have been reported, and emerging evidence from recent trials suggests that CART cell therapies may prove effective in relapsed/refractory PTCL. The recommended treatment strategy in non-ALK+ PTCL remains induction with a CHOP-like regimen followed by consolidative autoHCT in first remission. In the relapsed/refractory setting, salvage chemotherapy followed by HCT (autoHCT or alloHCT depending on histologic subtype and HCT history) offers the only potential for cure or long-term remission. Ample room for improvement remains in the treatment of patients with PTCL, and novel treatment strategies incorporating targeted agents and CAR-T therapy may help to address the unmet needs of this patient population.

Keywords: Adoptive cellular therapy; Anaplastic large cell lymphoma; Angioimmunoblastic lymphoma; Hematopoietic cell transplant; Peripheral T cell lymphoma; T cell non-Hodgkin lymphoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brentuximab Vedotin / therapeutic use
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / mortality
  • Induction Chemotherapy
  • Lymphoma, T-Cell, Peripheral / genetics
  • Lymphoma, T-Cell, Peripheral / immunology
  • Lymphoma, T-Cell, Peripheral / mortality
  • Lymphoma, T-Cell, Peripheral / therapy*
  • Receptors, Chimeric Antigen / immunology*
  • Salvage Therapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Histone Deacetylase Inhibitors
  • Receptors, Chimeric Antigen
  • Brentuximab Vedotin