Mycosis fungoides and Sezary syndrome are rare and largely incurable types of cutaneous T-cell lymphoma with limited therapeutic options. In 1984 Bunn et al. reported that interferon alpha is an... Show moreMycosis fungoides and Sezary syndrome are rare and largely incurable types of cutaneous T-cell lymphoma with limited therapeutic options. In 1984 Bunn et al. reported that interferon alpha is an efficient monotherapy in cutaneous T-cell lymphoma and 14 years later it was shown in a prospective, randomized trial that a combination of interferon alpha and psoralen plus ultraviolet A therapy (PUVA) is most efficient in the treatment of cutaneous T-cell lymphoma. Since then interferon alpha as single agent or, most often, in combination with phototherapy and/or retinoids has been integrated as standard of care in cutaneous T-cell lymphoma guidelines worldwide. However, production of interferon alpha was discontinued recently worldwide and pegylated interferon alpha-2a (PEG-IFN alpha) has been used as an alternative therapy. In contrast to numerous interferon alpha studies, only a few studies focusing on PEG-IFN alpha are available. Therefore, the aim of this study was to conduct a retrospective data collection to report on the efficacy, adverse events and therapy regimens of PEG-IFN alpha in cutaneous T-cell lymphoma. In 28 patients with cutaneous T-cell lymphoma treated in Germany and in the Netherlands, 36% of patients achieved complete remission, 36% partial remission and 29% stable disease. Eighteen percent of patients developed adverse events during therapy, which led to the discontinuation of PEG-IFN alpha therapy in 2 patients. The most common concomittant therapies were oral PUVA phototherapy and local radiotherapy. In conclusion, PEG-IFN alpha, especially in combination with skin-directed therapies, is an effective treatment option for cutaneous T-cell lymphoma in clinical practice. Show less
Background: Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is associated with a poor prognosis and severe symptoms. Objective: To establish insights into the quality of life (QoL), expectations,... Show moreBackground: Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is associated with a poor prognosis and severe symptoms. Objective: To establish insights into the quality of life (QoL), expectations, and treatment satisfaction of E-CTCL patients receiving mogamulizumab. Methods: Outcomes of this prospective cohort study conducted between September 2020 and August 2021 at the Leiden University Medical Center included the dermatology-specific QoL (Skindex-29), health-related QoL (RAND-12), degree of itch, pain, and fatigue (Visual Analogue Scale), patient’s expectations, and treatment satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8)), measured at baseline and after six months. Results: 13 patients with E-CTCL were included. Most patients anticipated a positive treatment effect on symptoms. Five patients (46%) improved one or more clinical categories regarding the symptoms domain, six (55%) regarding emotions, four (36%) regarding functioning, and four (36%) regarding the overall Skindex-29 score compared to baseline. The Mental Component Score clinically improved from 31 (IQR 29–51) at baseline to 38 (IQR 25–51). The median VAS itch improved significantly from baseline (8 (IQR 7–10) vs. 3 (IQR 1–8), p = 0.024). Most patients (n = 7) were “very satisfied” with their treatment. Limitations: There was a limited number of patients due to the rarity of the disease. Conclusion: In general, mogamulizumab has a favorable effect on biochemical- and dermatology-specific QoL and physical functioning in some patients, with high treatment satisfaction. Itch especially improved over time in most patients. The treatment satisfaction was generally high. Mogamulizumab seems to be an effective treatment that improves the QoL in patients with E-CTCL. Show less
Musiek, A.C.M.; Rieger, K.E.; Bagot, M.; Choi, J.N.; Fisher, D.C.; Guitart, J.; ... ; Kim, Y.H. 2021
The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed... Show moreThe CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sezary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event. The objective of this report was to combine results from published literature with experiences and recommendations from multiple investigators and institutions into clinical best practice recommendations to assist healthcare providers in identifying and managing mogamulizumab-associated rash. Optimal management, which includes biopsy confirmation and steroid treatment, requires a multidisciplinary approach among oncology, dermatology, and pathology practitioners. Show less
Y Cutaneous T-cell lymphomas and leukemias (CTCLs) are a heterogeneous group of extranodal non-Hodgkin's lymphomas. These are characterized by an accumulation of malignant CD4(+) T-lymphocytes in... Show moreY Cutaneous T-cell lymphomas and leukemias (CTCLs) are a heterogeneous group of extranodal non-Hodgkin's lymphomas. These are characterized by an accumulation of malignant CD4(+) T-lymphocytes in the skin, lymph nodes, and peripheral blood. Novel treatment options are needed for patients who progress to advanced stage disease. Cucurbitacin I has previously shown promising results in Sezary syndrome (Sz). A plethora of cucurbitacins, however, have not yet been tested in CTCL. Herein, we investigated the effect of cucurbitacin E and I in two CTCL cell lines. We show that both cucurbitacins decrease viability and cause apoptosis in these cell lines, although HuT-78 was more affected than SeAx (IC50 of 17.38 versus 22.01 mu M for cucurbitacin E and 13.36 versus 24.47 mu M for cucurbitacin I). Moreover, both cucurbitacins decrease viability of primary cells of a Sz patient (56.46% for cucurbitacin E and 59.07% for cucurbitacin I). Furthermore, while JAK2 inhibition leads to decreased viability in SeAx cells (IC50 of 9.98 and 29.15 mu M for AZD1480 and ruxolitinib respectively), both JAK1 and JAK3 do not. This suggests that JAK2 has a preferential role in promoting survival. Western blotting in SeAx cells revealed that both cucurbitacins inhibit STAT3 activation (P < 0.0001), while only cucurbitacin I inhibits STAT5 activation (P = 0.05). This suggests that STAT3 plays a preferential role in the mechanism of action of these cucurbitacins. Nevertheless, a role of STAT5 and JAK2 cannot be excluded and should be explored further. This knowledge could contribute to the development of effective therapies for CTCL and other malignancies involving dysfunction of the JAK/STAT pathway. Show less
Gru, A.A.; Kim, J.; Pulitzer, M.; Guitart, J.; Battistella, M.; Wood, G.S.; ... ; Kim, Y.H. 2018
