Mogamulizumab
Sources réglementaires consultées
Indications approuvées
- Mycosis fongoïde ou syndrome de Sézary en rechute ou réfractaire chez l’adulte après au moins un traitement systémique.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer une toxicité cutanée sévère ou mortelle, notamment un syndrome de Stevens-Johnson et une nécrolyse épidermique toxique. — DailyMed, POTELIGEO set_id e53960ab-42a1-40d1-9c7d-eb013fe7f18f
- Mise en garde majeure · Surveiller les réactions à la perfusion, les infections graves, les complications auto-immunes et la maladie du greffon contre l’hôte sévère ou mortelle après greffe allogénique. — DailyMed, POTELIGEO set_id e53960ab-42a1-40d1-9c7d-eb013fe7f18f
Effets indésirables
Communs (≥1%)
éruption cutanée · réaction à la perfusion · fatigue · diarrhée · douleur musculosquelettique · infection des voies respiratoires supérieures
Rares mais graves
syndrome de Stevens-Johnson ou nécrolyse épidermique toxique · infection grave · complication auto-immune · maladie du greffon contre l’hôte mortelle
Grossesse et allaitement
Il n’est pas recommandé pendant la grossesse. Vérifier la grossesse avant le traitement et utiliser une contraception efficace pendant le traitement et pendant 3 mois après. Pendant l’allaitement, décider de poursuivre l’allaitement ou le traitement selon le bénéfice et le risque.
Bibliographie récente (PubMed)
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
Cutaneous T-cell lymphomas (CTCLs) are a group of rare and heterogenous diseases. There is currently no curative treatment for patients with advanced mycosis fungoides (MF) and Sézary syndrome (SS). The European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of MF/SS have been updated and focus on recently available treatments. Peginterferon, a new form of interferon, has a favourable risk-benefit profile for the treatment of patients with CTCL. Recently approved monoclonal antibodies (mABs) have completely modified the treatment algorithm of advanced CTCL treatment. Brentuximab vedotin is very efficient for tumours and transformed MF. Mogamulizumab can induce long-term remission in patients with SS. An international trial of lacutamab has recently been completed, for both SS and MF. Numerous novel targets have been identified, and several new mABs have been shown to be able to enhance specific immune responses and to induce targeted antibody-dependent cytotoxicity and cytophagocytosis. These new antibodies warrant further evaluation in controlled trials. Kinase inhibitors and chimeric antigen receptor T-cell therapy are promising new treatments. Finally, recent studies have demonstrated that allogeneic haematopoietic stem-cell transplantation can increase survival and quality of life in patients with advanced CTCL. Cutaneous T-cell lymphomas (CTCLs) are rare skin cancers. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of CTCL. Currently, there is no cure for advanced forms of these diseases. New treatment guidelines reflect recent advances in therapy for CTCLs. For example, peginterferon is a newer form of interferon, which has shown promise in treating CTCL. It offers a balance between effectiveness and safety. New treatment options have greatly changed how advanced CTCL is treated. Brentuximab vedotin is very effective for certain types of MF, particularly the more aggressive forms. Mogamul
No standard of care for older patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 2 weeks with mogamulizumab (Moga; Moga-CHOP-14) for older patients with untreated ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56 to 65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. The primary end point was 1-year progression-free survival (PFS). Secondary end points were the complete response (CR) rate, overall response rate (ORR), overall survival (OS), 1-year event-free survival (EFS), and safety. We also investigated the impact of CC chemokine receptor 4 (CCR4) mutation and Moga-associated cutaneous adverse events (cAEs) on PFS and OS. The study protocol was amended to allow the dosing interval to be extended to 21 days at the physician's discretion. Among 48 evaluable patients, the 1-year PFS was 36.2% (90% confidence interval, 24.9-47.6), with a median follow-up of 1.6 years. The 1-year OS and EFS were 66.0% and 29.9%, respectively. CR and ORR were 64.6% and 91.7%. No unexpected toxicities were observed. Of 47 patients who received ≥2 cycles of CHOP, 20 (42.6%) received CHOP-14, among whom 12 (25.5%) completed 6 cycles. CCR4 mutation and Moga-associated cAEs were associated with better OS. This study showed that Moga-CHOP significantly improved PFS, although the optimal interval for CHOP remains undetermined. Moga-CHOP is now considered a preferable first-line treatment for this patient population. This trial was registered at https://jrct.mhlw.go.jp/en-top as #jRCTs041180130.
Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a lifelong asymptomatic balance between infected cells and host antiviral immunity; however, 5-10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of HTLV-1 pathogenicity. As CD4+ T cells play a central role in host immunity, the deregulation of their function and differentiation via HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs the immunological balance. Various approaches are available for treating these abnormalities; however, hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL. The patient's immune state may contribute to the treatment outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, depends on immune function, including antibody-dependent cytotoxicity. In this comprehensive review, we summarize the immunopathogenesis of HTLV-1 infection in ATL and discuss the clinical findings that should be considered when developing treatment strategies for ATL.