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Non-Hodgkin Lymphoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Piers Blombery, David C. Linch
PTCL-NOS—PTCL-NOS accounts for around half of the cases of PTCL in Western countries.84,85,106 It is a heterogeneous group of diseases with a predominantly nodal presentation. Genomic characterization of this broad biological group has identified three major subgroups within PTCL-NOS: (i) PTCL-GATA3 which overexpresses GATA3 and has an inferior prognosis, (ii) PTCL-TBX21 which overexpresses TBX21, and (iii) PTCL-TFH which is a nodal PTCL-NOS that expresses a TFH phenotype (CD4+, PD1+, CD10+, BCL6+ CXCL13, and/or ICOS).96 The overall prognosis is variable reflecting the biological heterogeneity of the underlying disorder, ranging from a 5-year OS under 20% in the highest-risk patients to approximately 60% in patients without adverse risk factors.83 Although optimal frontline therapy is unclear, CHOP-type chemotherapy is usually used (with the addition of etoposide possibly adding benefit).90 In addition, there have been attempts to add targeted therapy to CHOP regimens analogous to the addition of rituximab to CHOP in the treatment of B-lineage NHL. CHOP-alemtuzumab,107 CHOP-bortezomib,108 and CHOP-denileukin diftitox109 have all been trialed with varying success. One potential option for CD30-expressing PTCL-NOS is BV-CHP.91
Non-Hodgkin lymphoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Piers Blombery, Adrian Bloor, David C. Linch
PTCL-NOS – PTCL-NOS accounts for around half of the cases of PTCL in Western countries.108,109,136 It is a heterogeneous group of diseases with a predominantly nodal presentation. The overall prognosis is variable reflecting the biological heterogeneity of the underlying disorder, ranging from a 5-year OS under 20% in the highest-risk patients to approximately 60% in patients without adverse risk factors.107 Although optimal front-line therapy is unclear, CHOP-type chemotherapy is usually used (with the addition of etoposide appearing to add benefit114). In addition, there have been attempts to add targeted therapy to CHOP regimens analogous to the addition of rituximab to CHOP in treatment of B-lineage NHL. CHOP-alemtuzumab,137 CHOP-bortezomib138 and CHOP-denileukin diftitox139 have all been trialled with varying success.
Aptamers and Cancer Nanotechnology
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Omid C. Farokhzad, Sangyong Jon, Robert Langer
The feasibility of using antibodies for targeted therapy, particularly for oncologic diseases, has been demonstrated repeatedly in the literature. Rituximab (Rituxan™) was the first therapeutic based on monocloncal antibodies to receive FDA approval in 1997 for treating patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin’s lymphoma.27 A wide variety of antibody-based drugs are now under clinical development or are in clinical practice today. For example, denileukin diftitox (Ontak™) is an FDA-approved immunotoxin for the treatment of cutaneous T-cell lymphoma.28 Many other radioimmunoconjugates or chemoimmunoconjugates directed against cell surface antigens are currently in various stages of clinical and pre-clinical development. Despite the recent success of monoclonal antibodies as targeting moieties, the use of antibodies for drug targeting may have a number of potential disadvantages. First, antibodies are large molecules (~ 20 nm for intact antibodies)29,30 and their use in developing nanoscale therapeutic and diagnostic tools may result in an increase in vehicle size without added advantage. Second, antibodies may be immunogenic. Despite the current engineering approaches to yield improved humanized antibodies, this problem is not universally solved. Third, the biological development of monoclonal antibodies can be difficult and unpredictable. For example, the target antigen may not be well tolerated by the animal used to produce the antibodies, or the target molecules may be inherently less immunogenic, making it difficult to raise antibodies against such targets (although, this problem is overcome with the use of phage display libraries).31,32 Fourth, the production of antibodies involves a biological process that can result in batch-to-batch variability in their performance, particularly when production is scaled up. The ideal targeting molecule for the delivery of nanoscale therapeutic and diagnostic systems should, like monoclonal antibodies, bind with high affinity and specificity to a target antigen but overcome or ameliorate some of the problems associated with the use and production of monoclonal antibodies.
The clinical and humanistic burden of cutaneous T-cell lymphomas and response to conventional and novel therapies: results of a systematic review
Published in Expert Review of Hematology, 2020
Mehul Dalal, Stephen Mitchell, Conor McCloskey, Erin Zagadailov, Ashish Gautam
The length of PFS was reported for 14 different interventions and median PFS ranged from 3.1 months to 116.4 months across studies for vorinostat and brentuximab vedotin, respectively [52,61] (Figure 4). A PFS of >20 months was reported only for the investigational therapies brentuximab vedotin (range: 15.8–116.4 months) [57,61,62] and alemtuzumab (56 months) [33]. Considerable variation was observed in PFS where it was reported in multiple studies for a single intervention. The greatest variation was for brentuximab vedotin for which PFS ranged from 15.8 months to 116.4 months [57,61]. Variation in PFS was also observed between studies following treatment with bexarotene combination therapies (range: 5.3–12.8 months) [63,64], denileukin diftitox (range: 6.7–32 months) [54,65], and mogamulizumab (range: 5.2–11.4 months) [66,67]. Time to tumor progression was reported for six different CTCL therapies (supplementary material): <5 months for belinostat and alemtuzumab [33,55]; 5–8 months for romidepsin, vorinostat, and pegylated liposomal doxorubicin [59,68–72]; and 11 months for bexarotene [73]. Median OS was reported for 12 different therapies and ranged from 13.7 to 72 months following treatment with mogamulizumab or ECP, respectively (Supplementary material) [67,74].
The efficacy and safety of methotrexate versus interferon in cutaneous T-cell lymphomas
Published in Journal of Dermatological Treatment, 2018
Thevaki Wain, Alexandra Pavli, Jillian Wells, Pablo Fernandez-Peñas
MTX and IFN have been used in the management of CTCLs either as monotherapy or in combination with other documented therapies (3,14–16). In Australia, not all therapies reported to be effective for CTCL are available for patients. Bexarotene, a retinoid used either topically or orally, and Pralatrexate, second generation antifolate, with proven efficacy in management of CTCL are not available in Australia (17–19). To date, ECP, used in severe disease, is only available in a single center nationwide for the indication of lymphoproliferative cutaneous malignancies (20). Psoralen with ultraviolet A treatment, another staple in the management of this disease, is not accessible in most dermatology centers (21). Targeted therapies such as histone deacetylase inhibitors and alemtuzumab are not widely prescribed in most outpatient dermatology settings and often require co-management with hematologists in multidisciplinary settings (22–24). Finally, novel agents such as denileukin diftitox are only currently being prescribed in specialized research centers in Australia with vast majority of patients still unable to access these therapies (25). Thus in Australia, MTX and IFN are much more widely used in the setting of CTCL due to ease of access, low costs and ease of dosing than in other parts of the world.
The use of immunotherapy for the treatment of tuberculosis
Published in Expert Review of Respiratory Medicine, 2018
Octavio Ramos-Espinosa, León Islas-Weinstein, Marco Polo Peralta-Álvarez, Manuel Othoniel López-Torres, Rogelio Hernández-Pando
Suppressor cell-depleting therapies are another feasible alternative. Denileukin diftitox (DD) is a fusion protein (IL-2/diphtheria toxin) employed for treating cutaneous lymphomas by targeting cells expressing CD25+, specifically regulatory T cells (Treg). Treg cells have been shown to antagonize the protective immune response against TB, thus preventing bacterial clearance. In a murine model of TB, DD reduced Treg populations and bacterial burdens in lungs and spleen. This effect was observed either as a monotherapy and in combination with standard treatment [131].