Novel targeted therapies of T cell lymphomas

Abstract

T cell lymphomas (TCL) comprise a heterogeneous group of non-Hodgkin lymphomas (NHL) that often present at an advanced stage at the time of diagnosis and that most commonly have an aggressive clinical course. Treatment in the front-line setting is most often cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens, which are effective in B cell lymphomas, but in TCL are associated with a high failure rate and frequent relapses. Furthermore, in contrast to B cell NHL, in which substantial clinical progress has been made with the introduction of monoclonal antibodies, no comparable advances have been seen in TCL. To change this situation and improve the prognosis in TCL, new gene-targeted therapies must be developed. This is now possible due to enormous progress that has been made in the last years in the understanding of the biology and molecular pathogenesis of TCL, which enables the implementation of the research findings in clinical practice. In this review, we present new therapies and current clinical and preclinical trials on targeted treatments for TCL using histone deacetylase inhibitors (HDACi), antibodies, chimeric antigen receptor T cells (CARTs), phosphatidylinositol 3-kinase inhibitors (PI3Ki), anaplastic lymphoma kinase inhibitors (ALKi), and antibiotics, used alone or in combinations. The recent clinical success of ALKi and conjugated anti-CD30 antibody (brentuximab-vedotin) suggests that novel therapies for TCL can significantly improve outcomes when properly targeted.

Keywords: Alki; Antibodies; CART; HDACi; PI3Ki; PTCL; SPTCL; TCL; Targeted therapy.

Fig. 1

Targeted T cell lymphoma therapies mode of action. ADCC: Antibody-dependent cellular cytotoxicity, CD: cluster of differentiation antigens CDX: CD16, CD25, CD30, CD38, CD47, CD52, KIR3DL2 (CD158k), CCR4 (CD194), ICOS (CD278), CAMD1; CDY: CD4, CD5, CD7, CD30, HDAC: histone deacetylase, ALK: anaplastic lymphoma kinase, PI3K: phosphoinositide 3-kinases, BCL11B: B cell lymphoma/leukemia 11B

Fig. 2

Targeted therapies in T cell lymphoma subtypes. AITL—angioimmunoblastic T cell lymphoma, CTCL—cutaneous T cell lymphoma, PTCL—peripheral T cell lymphoma, T-LBL/ ALL—T cell lymphoblastic lymphoma/T cell acute lymphoblastic leukemia, ALCL—anaplastic large-cell lymphoma, ATLL—adult T cell leukemia/lymphoma, ENKTL—extranodal NK/T cell lymphoma