The Updated Scope of Dermato Gambichler, Thilo; Assaf, Chalid
Dermato,
03/2024, Letnik:
4, Številka:
2
Journal Article
Recenzirano
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We are very happy that Dermato has now entered its fourth year, having published notable papers covering the wide field of dermatology and other closely related disciplines ...
Research in cutaneous T-cell lymphoma has widened from the malignant T cell itself to the tumor microenvironment. In this issue of the Journal of Investigative Dermatology, Aronovich et al. (2020) ...report the presence of cancer-associated fibroblasts (CAFs) in mycosis fungoides (MFs). They show that CAFs are abundant in early-stage MF and that they differ from normal fibroblasts. Moreover, CAFs are described to promote MF by increasing the motility and chemoresistance of malignant T cells. Thus, targeting CAFs in MF may be of therapeutic value.
Multiple myeloma is a lymphoproliferative disease, which rarely presents with skin involvement or associated symptoms. Better awareness of these dermatological presentations is required for early ...diagnosis and to guide the patient towards appropriate therapy. We report on a patient with diffuse filiform hyperkeratosis and immunoglobulin-associated vasculitis in a severe progression of a known myeloma.
PURPOSE This phase III, placebo-controlled, randomized trial was designed to investigate efficacy and safety of two doses of denileukin diftitox (DD; DAB(389)-interleukin-2 IL-2), a recombinant ...fusion protein targeting IL-2 receptor-expressing malignant T lymphocytes, in patients with stage IA to III, CD25 assay-positive cutaneous T-cell lymphoma (CTCL), including the mycosis fungoides and Sézary syndrome forms of the disease, who had received up to three prior therapies. The primary end point was overall response rate (ORR). PATIENTS AND METHODS Patients (N = 144) with biopsy-confirmed, CD25 assay-positive CTCL were randomly assigned to DD 9 microg/kg/d (n = 45), DD 18 microg/kg/d (n = 55), or placebo infusions (n = 44), administered for 5 consecutive days every 3 weeks for up to eight cycles. Patients were monitored for drug efficacy, clinical benefit, and safety of DD. RESULTS ORR was 44% for all participants treated with DD (n = 100; 10% complete response CR and 34% partial response PR) compared with 15.9% for placebo-treated patients (2% CR and 13.6% PR). ORR was higher in the 18 microg/kg/d group versus the 9 microg/kg/d group (49.1% v 37.8%, respectively), and both doses were significantly superior to placebo. Progression-free survival (PFS) was significantly longer (median, > 2 years) for both DD doses compared with placebo (median, 124 days; P < .001). Rates of moderately severe and severe adverse events (AEs) were slightly higher in the DD groups, whereas moderate and mild AEs were similar to placebo. No statistical differences were observed for drug-related serious AEs. CONCLUSION DD had a significant and durable effect on ORR and PFS with an acceptable safety profile in patients with early- and late-stage CTCL.
Cutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical ...derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative.
Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As curative approaches apart from ...allogeneic stem cell transplantation are lacking, establishing new treatment options, especially combination therapies, is crucial.
This retrospective study included 11 patients with SS or MF receiving therapy with mogamulizumab in combination with ECP from four European expert centers. The response rates in the skin and blood as well as treatment use and adverse events (AE) were described.
8/11 patients (73%) showed an overall response (OR) in the skin. The mean mSWAT decreased from 98.2 ± 40.8 to 34.6 ± 23.8. The overall response rate (ORR) in the blood was 64% with two complete responses. During combination therapy, the mean number of Sézary cells decreased from 3365.3 × 10
/L before treatment to 1268.6 × 10
/L. The mean minimum known period without progress was 7.2 months in the skin and 7.6 months in the blood. The most common AEs were mogamulizumab-associated rash (MAR) (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion related reaction (16.7%). No AE led to treatment discontinuation.
Our study presents the combination of mogamulizumab and ECP as an effective therapy in the blood and skin in CTCL with good tolerability, similar to mogamulizumab monotherapy.
Purpose
Total skin electron beam therapy (TSEBT) has proved to be a safe and effective treatment for cutaneous T‑cell lymphomas. Here, we examined the impact of this treatment on patient quality of ...life and outcome.
Patients and methods
Forty-four patients with mycosis fungoides (MF) or Sezary syndrome (SS) received 48 TSEBT courses with a median dose of 12 Gy within the past 8 years at our institute. Patient and treatment characteristics for these cases as well as the impact of TSEBT on quality of life and duration of response were retrospectively analyzed and compared.
Results
The median modified Severity-Weighted Assessment Tool score before the start of TSEBT was 44. The overall response rate was 88%, with a complete response (CR) rate of 33%. The median follow-up period was 13 months. The median duration of response (DOR) and progression-free survival (PFS) for the entire cohort were 10 months and 9 months, respectively. Patient-reported symptom burden was measured with the Dermatological Life Quality Index and Skindex-29 questionnaires. The mean symptom reductions were 6 ± 8 (
P
= 0.005) and 21 ± 24 (
P
= 0.002), respectively. In the Functional Assessment of Cancer Therapy-General Assessment, significant improvements in the emotional (
P
= 0.03) domains were observed after TSEBT. Patients who received maintenance or adjuvant treatments had a longer PFS (
P
= 0.01).
Conclusion
TSEBT improved disease symptoms and significantly improved emotional domains of patients’ quality of life in patients with MF or SS. In addition, our results indicate that maintenance or adjuvant therapy after TSEBT may improve the PFS.
Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is ...significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.
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