Thus, mogamulizumab-containing treatment was unable to overcome treatment refractoriness of ATLL with NOTCH1 alterations. Therefore, patients with NOTCH1 alterations are recommended for allogeneic-HSCT.
Univariate analysis identified comorbidity as a predictor of poor outcomes, but not intensity of MOG-containing treatment, suggesting a different mechanism of action than that of classical chemotherapy. Our study suggests that MOG-containing treatments are an option for elderly patients with ATL.
We propose that this combination may be a treatment option for patients with SS. Further research is needed to understand the efficacy and tolerability profile of this therapeutic combination and to determine if there is an additive effect of the combination on the response rates when compared with the monotherapy.
Mogamulizumab, an FDA-approved anti-CCR4 antibody, has shown efficacy in treating MF/SS; however, its side effects have raised concerns, underscoring the need for more effective and less toxic CCR4-targeted therapies...Furthermore, only C021 inhibited tumor growth in CTCL xenograft mice in vivo. These findings suggest that Class I CCR4 antagonists such as C021 exerts more potent anti-tumor effects on CTCL cells in vitro and in vivo compared to Class II CCR4 antagonists like AZD2098, highlighting its potential for clinical application.
In patients with CD30-expressing CTCL, Brentuximab Vedotin has demonstrated better response rates and progression-free survival (PFS); in advanced SS, mogamulizumab has significantly increased PFS. These findings emphasize the need to standardize prognostic factors and improve CTCL treatment.
Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy...We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.
We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment...Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.
5 months ago
Clinical • Observational data • Retrospective data • Journal
P2, N=38, Terminated, RAPT Therapeutics, Inc. | N=100 --> 38 | Trial completion date: Aug 2025 --> Jun 2024 | Suspended --> Terminated | Trial primary completion date: Jun 2025 --> Jun 2024; Study on clinical hold by FDA
5 months ago
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.
This review also provides an introduction to protein structures of CXCL12 and CXCR4 and the application of computer simulation and analysis in understanding CXCR4 activation and antagonist binding. Furthermore, examples of strategies and current progress in CXCL12-CXCR4 axis-targeted development of therapeutic anticancer inhibitors are discussed.
Mogamulizumab's ability to augment the host immune response through Treg depletion adds to its efficacy but has wide-ranging implications for autoimmunity across multiple organ systems, similar to immune checkpoint inhibitor therapy. Occurrence of irAEs may be associated with improved overall clinical response, although long-term follow-up studies are needed.
CCL2 mRNA was expressed in all glioma cell lines and expression increased when exposed to Tregs but not to CD4 + helper T-cells. Conclusion Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.
This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
6 months ago
Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
P2, N=229, Terminated, RAPT Therapeutics, Inc. | Trial completion date: Sep 2024 --> May 2024 | Suspended --> Terminated; Study on clinical hold by FDA
The safety and effectiveness of mogamulizumab for PTCL and CTCL in the real world were comparable with the data reported in previous clinical trials. Clinical Trial Registration.
P1/2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jun 2025 | Trial primary completion date: Dec 2025 --> Jun 2025
7 months ago
Trial completion date • Trial primary completion date • Combination therapy • Immune cell
Even after mogamulizumab administration, which shows potent effects for peripheral blood lesions, the N fraction was still a useful indicator for prognostic estimation. In summary, this report shows that CADM1 versus CD7 plots in CD4+ T cells are useful indicators of the clinical course and prognosis of aggressive ATL. Therefore, this CADM1 and CD7 profile is suggested to be a useful prognostic indicator consistently from HTLV-1 carriers to aggressive ATL.
Continued research aims to optimise treatments, enhance outcomes, and transform CTCL management. This review aims to elucidate the biological rationale and the several agents under various stages of development and clinical evaluation with the actual known data.
Side effects can manifest themselves in all organ systems. Chronic side effects and long-term harm are possible, especially with ICIs, and require close therapy monitoring and patient education. Knowledge of the side effects and the temporal, sometimes delayed course of their occurrence are essential for diagnosis and prompt initiation of therapy.
Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential.
The patient developed severe gastrointestinal acute GvHD, which was treated with steroids and infliximab. Further research is required to fully understand the interaction between mogamulizumab and allo-HCT and to determine whether it is an optimal approach as a bridge to transplant therapy. This paradigmatic case suggests the need of personalizing transplant strategies by selecting appropriate conditioning therapy and GvHD prophylaxis to minimize potential toxicity.
Fourteen patients with known GVHD underwent transplantation between 50 and 365 days after their last dose of mogamulizumab, while 2 underwent transplantation within 50 days after treatment. Based on this limited evidence, GVHD was not associated with the time interval from last mogamulizumab dose to transplantation.
Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML.
Importantly, residual CD4+ T cells following Sézary cell ablation lacked any immunologic shifts. These findings collectively unveil an auxiliary role for augmenting monocytic activity during mogamulizumab therapy in the treatment of SS and underscore the importance of targeted combination therapy in this disease.
Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.
Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model...The depletion of CCR4+ cell and CD25+ cell (two target cell populations of CCR4-IL2-IT) was observed in minipigs. The excellent safety profile promoted us to further develop CCR4-IL2-IT towards clinical trials.