Dataset Information

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

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.

SUBMITTER: Rogers AM

PROVIDER: S-EPMC7415649 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.

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Dataset Information

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

Purpose of review

Recent findings

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