-
Cancer Biology & Medicine Feb 2021Natural killer/T-cell lymphoma (NKTCL) is a highly invasive subtype of non-Hodgkin lymphoma, typically positive for cytoplasmic CD3, CD56, cytotoxic markers, including... (Review)
Review
Natural killer/T-cell lymphoma (NKTCL) is a highly invasive subtype of non-Hodgkin lymphoma, typically positive for cytoplasmic CD3, CD56, cytotoxic markers, including granzyme B and TIA1, and Epstein-Barr virus (EBV). The current treatment methods for NKTCL are associated with several drawbacks. For example, chemotherapy can lead to drug resistance, while treatment with radiotherapy alone is inadequate and results in frequent relapses. Moreover, hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts. In recent years, immunotherapy has shown good clinical results and has become a hot spot in cancer research. Clinical activity of targeted antibodies, such as daratumumab (anti-CD38 antibody) and brentuximab vedotin (anti-CD30 antibody), have been reported in NKTCL. Additionally, dacetuzumab and Campath-1H have demonstrated promising results. Further encouraging data have been obtained using checkpoint inhibitors. The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL. Furthermore, anti-CCR4 monoclonal antibodies (mAbs) exert cytotoxic actions on both CCR4+ tumor cells and regulatory T cells. Depletion of these cells and the long half-life of anti-CCR4 mAbs result in enhanced induction of antitumor effector T cells. The role of IL10 in NKTCL has also been investigated. It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies. Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission. Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease. The present review outlines the known immunotherapy targets for the treatment of NKTCL.
Topics: Alemtuzumab; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B7-H1 Antigen; Brentuximab Vedotin; Herpesvirus 4, Human; Humans; Immunotherapy; Lymphoma, Extranodal NK-T-Cell; Natural Killer T-Cells; T-Lymphocytes, Cytotoxic
PubMed: 33628584
DOI: 10.20892/j.issn.2095-3941.2020.0400 -
BMC Cancer Dec 2020The purpose of this network meta-analysis of randomized controlled trials (RCTs) was to compare rank targeted therapies for patients with diffuse large B-cell lymphoma... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this network meta-analysis of randomized controlled trials (RCTs) was to compare rank targeted therapies for patients with diffuse large B-cell lymphoma (DLBCL).
METHODS
The PubMed, EmBase, and Cochrane library electronic databases were systematically searched throughout December 2019. Direct and indirect evidence from relevant RCTs was identified for network meta-analysis. The pooled results for grade 3 or greater adverse events between targeted therapies and chemotherapy were calculated using a random-effects model.
RESULTS
A total of 18 RCTs enrolling 8207 DLBCL patients were selected for the final meta-analysis. The results of the network analysis indicated that the addition of dacetuzumab (74.8%) to rituximab-based regimens or lenalidomide (77.1%) was associated with better therapeutic effects on overall survival, whereas dacetuzumab (80.4%) or bortezomib (70.8%) added to rituximab was most likely to improve events-free survival. Moreover, lenalidomide (93.8%) and I-tositumomab (77.2%) were associated with higher overall response rates. Finally, patients receiving targeted therapies were associated with an increased risk of diarrhea (RR: 2.63; 95%CI: 1.18-5.86; P = 0.019), and thrombocytopenia (RR: 1.41; 95%CI: 1.05-1.90; P = 0.023).
CONCLUSIONS
This study provides the best treatment strategy for DLBCL patients in terms of overall survival, events-free survival, and overall response rate. The findings of this study require validation with further large-scale RCTs.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Humans; Lymphoma, Large B-Cell, Diffuse; Molecular Targeted Therapy; Prognosis; Survival Rate
PubMed: 33308179
DOI: 10.1186/s12885-020-07715-2 -
Frontiers in Oncology 2020Primary cutaneous B-cell lymphomas (pCBCL) include an infrequent group of non-Hodgkin lymphomas that are limited to skin sites at the time of diagnosis. They comprise... (Review)
Review
Primary cutaneous B-cell lymphomas (pCBCL) include an infrequent group of non-Hodgkin lymphomas that are limited to skin sites at the time of diagnosis. They comprise roughly 20-25% of all cutaneous lymphomas and are subdivided into primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large cell B cell lymphoma, leg type (PCDLCBCL, LT). The first two show a rather indolent course while PCDLCBCL, LT carries a worse prognosis. Intravascular large cell B-cell lymphoma is the most infrequent subtype, and its therapy is not covered in this review. For solitary, single-site PCMZL and PCFCL, several topical treatment options exist. They include, but are not limited to, excision, radiotherapy, and intralesional therapies, discussed in this review. However, in selected cases, even "watchful waiting" is reasonable. Indolent types of pCBCL rarely require systemic treatment. However, in extended cases and more importantly DLCBCL, LT, systemic treatment is the first choice. Monoclonal anti-CD20-antibody rituximab is often used as monotherapy in PCMZL and PCFCL or combined with chemotherapy in PCDLBCL, LT. Newer options are monoclonal anti-CD40 antibody dacetuzumab, anti-PD-1 and anti-PD-L1 checkpoint inhibitors, and Bruton tyrosine kinase inhibitors. Indolent pCBCL are treated with a risk-adapted strategy using intralesional steroids, RT, and interferon-α as first-line treatments. Relapsing cases may profit from rituximab. In aggressive PCDLCBCL, LT, rituximab with polychemotherapy is recommended. Innovative therapies include intralesional oncolytic virotherapy, systemic monoclonal antibodies, and small molecules.
PubMed: 32850331
DOI: 10.3389/fonc.2020.01163