Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study.

BACKGROUND: Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T-cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF). OBJECTIVES: The real-world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF). METHODS: In this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres. The overall response rate (ORR) under treatment was described (primary criterion), as well as treatment use and safety data. RESULTS: The 122 analysed patients (69 SS, 53 MF) were aged 66.6 ± 12.1 years at mogamulizumab initiation, and their median disease duration was 2.5 years (IQR: 1.3-5.6). Prior to treatment start, they received a median of three systemic CTCL therapies (2-5). Overall, 77.8% of patients suffered from advanced disease (Stage IIB-IVB), with frequent blood (B1/B2) involvement (67.5%). Over the treatment period (median: 4.6 months, 2.1-7.2), 96.7% of patients received all the planned mogamulizumab infusions. Among the 109 patients evaluable for effectiveness, ORR was 58.7% (95% CI [48.9-68.1]) overall, 69.5% [56.1-80.8] in SS and 46.0% [31.8-60.7] in MF. Compartmental response in the blood was observed in 81.8% [69.1-90.9] of SS patients. Skin responses were observed in 57.0% [47.0-66.5] of patients overall, 66.7% [52.9-78.6] in SS and 46.0% [31.8-60.7] in MF. The most common serious adverse drug reactions were rash (8.1% of patients) and infusion-related reactions (2.4%) which led to treatment discontinuation in 7.3% and 0.8% of patients, respectively. One patient with SS died from mogamulizumab-related tumour lysis syndrome. CONCLUSIONS: This large French study confirmed the effectiveness and tolerability of mogamulizumab in SS and MF patients in routine medical practice.

International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

[Panniculitis during BRAF inhibitor and/or MEK inhibitor therapy: A new case report and literature review]. / Hypodermite sous inhibiteur de BRAF et/ou inhibiteur de MEK : revue de la littérature à partir d'une nouvelle observation.

INTRODUCTION: BRAF inhibitors±MEK inhibitors can cause panniculitis. Since the initial case described in 2012 by Zimmer et al., some sixty further cases have been reported. Based on a clinical study and a recent and complete review of the literature, we set out in detail the characteristics of panniculitis occurring during BRAF and MEK inhibition therapy as well as the treatment thereof. PATIENTS AND METHODS: A 25-year-old-patient followed for multi-metastatic melanoma and taking dabrafenib and trametinib consulted for the appearance, twenty-two days after the start of targeted therapy (TT), of panniculitis of the legs and forearms possibly induced by the TT after other causes had been ruled out. The TT had been continued following dose reduction and corticoid therapy for ten days, and complete resolution occurred after fifteen days. RESULTS: Fifty-three cases of panniculitis during BRAF±MEK inhibition therapy were analysed. The condition occurred mainly with BRAF inhibitors alone (especially vemurafenib), but it was also described with three combinations of BRAF and MEK inhibitors, regardless of age (median: 45 years), with a M/F ratio of 0.51, and in 50 % of cases, it occurred within the first month (time to onset: between 1 and 480 days). Non-specific biopsy is useful to rule out differential diagnoses. Symptomatic anti-inflammatory treatment, whether systemic or topical, may be given. In the absence of signs of severity, the TT may be continued. CONCLUSION: When panniculitis occurs during BRAF±MEK inhibitor therapy, the causal role of the TT must be considered after full etiological investigation. It is essential to determine whether a causal relationship exists in order to avoid unwarranted cessation of treatment.

[Mycosis fungoides bullosa: A rare clinical presentation]. / Mycosis fongoïde bulleux : une présentation clinique exceptionnelle.

INTRODUCTION: Mycosis fungoides (MF) is the most common form of cutaneous lymphoma and usually manifests as erythematous and scaly patches or plaques. Its phenotypic or histologic presentation can be heterogeneous. Herein we report a very rare form of MF bullosa. PATIENTS AND METHODS: A 73-year-old man presented with a 4-month history of erythematous, scaly and itchy plaques on the trunk, as well as blistering lesions present for 2 months and which appeared on the trunk and lower limbs, both on patches of MF and on apparently healthy skin. Histopathology confirmed the diagnosis of bullous mycosis fungoides. Gene rearrangement of TCR showed a monoclonal profile in the skin. The hypothesis of bullous pemphigoid was ruled out by additional exams. Our patient was successively treated with combined interferon, bexarotene and methotrexate, followed by vorinostat, resulting in partial remission. DISCUSSION: Cases of bullous MF are very rare. In the literature, the clinical presentation is heterogeneous, with tense or flaccid bullae that can occur on unaffected skin or on erythematous plaques. The bullae generally appear after the plaques. The histologic blister site may be subepidermal or, more rarely, intra-epidermal. The exact mechanism of blister formation is not clear. Its treatment is poorly codified but follows the usual treatment of MF in its classical form. CONCLUSION: Bullous MF is a very rare entity that can mimic autoimmune blistering disease, and this diagnosis must therefore be ruled out.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

TOXICAN: a guide for grading dermatological adverse events of cancer treatments.

PURPOSE: The dermatological toxicity of cancer treatments is frequent and sometimes debilitating. Its reference classification, the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), is sometimes difficult to use and does not include yet the newest toxicities. Our objective was to create a guide, TOXICAN, based on the CTCAE, which is easy to use in everyday practice and which facilitates the recognition and grading of these dermatological toxicities. METHODS: This guide was developed by a working group ("GESTIM") comprising oncodermatologists, allergists, pathologists, and researchers from Nantes University Hospital. It was based on the dermatological toxicities found in the CTCAE and adapted to daily practice. These toxicities were grouped into categories and associated with photographs of typical cases to aid recognition. A simplified grading scale derived from the CTCAE was also created. This booklet was validated by means of user evaluation, and then the Delphi consensus method. RESULTS: We selected 32 dermatological toxicities, including 12 created by our group, sorted into 7 categories: skin rash, dry skin/pruritus, hyperkeratotic papules, palmoplantar changes, hair and nail changes, mucosal changes, and others. Our simplified grading scale only differed from the CTCAE for one item, urticaria. Three items were modified after evaluation by the user group and 11 after application of the Delphi method. CONCLUSION: The objective of our practical guide is to facilitate the use of the CTCAE for recognizing and grading dermatological toxicity of cancer treatments in order to provide optimal guidance for therapeutic adaptations. Its impact on clinical practice remains to be evaluated.

Changes in quality of life after a diagnosis of cancer: a 2-year study comparing breast cancer and melanoma patients.

PURPOSE: Longitudinal studies addressing change in health-related quality of life (HRQoL) following a diagnosis of cancer have mainly focused on a single cancer type, and little is known about the differences in HRQoL over time according to the type of tumor. The current study aims to compare the change in HRQoL over 2 years following breast cancer or melanoma diagnosis and socio-demographic variables associated with HRQoL over time. METHODS: Patients recently diagnosed with breast cancer (n = 215) or melanoma (n = 78) completed surveys within 1 month of diagnosis and 6, 12, and 24 months later. Multilevel modeling analyses were used to compare the evolution over time of HRQoL dimensions, as measured by the EORTC QLQ-C30, in both cancers. Longitudinal effect of socio-demographic variables on HRQoL was also assessed. RESULTS: Consistent with the literature, both cancer patients experienced decreased HRQoL scores following the diagnosis before improving over time. However, our analyses revealed that this rebound effect may occur at diverse times over the course of the illness according to the type of cancer. In addition, HRQoL over time was positively associated with age and negatively related to living with a partner regardless of the type of cancer. CONCLUSIONS: The results of the present study suggest that support in hospital units should be specific and depend on the cancer type.

Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab.

UNLABELLED: Ipilimumab is a monoclonal antibody blocking the inhibitory molecule CTLA4 expressed by activated T lympocytes, used for the treatment of metastatic melanoma. Recent studies have shown its potential efficacy on brain metastases. OBJECTIVES: To assess the development of brain metastases under ipilimumab and identify clinical, histological or evolving criteria related to the appearance of these metastases. A retrospective study was conducted in 52 patients treated with 4 cycles of ipilimumab 3 mg/kg every 3 weeks for unresectable stage III or stage IV melanoma between January 2011 and July 2013 in a Department of Dermato-Oncology. As no data has been find in the literature, the results were compared to our other cohort of patients treated with vemurafenib during the same period. Ten patients (21.7 %) developed brain metastases under ipilimumab in a median time of 6.58 months after treatment initiation. The multivariate analysis showed a lower rate of brain metastases in patients with acral lentiginous melanoma and melanoma of unknown primary site. The median survival after diagnosis of brain metastases was of 2.5 months. There was no significant difference with vemurafenib-treated patients in terms of incidence rate of brain metastasis, time of development and survival after diagnosis of cerebral metastases. This was the first study focused on the development of brain metastases under treatment with ipilimumab 3 mg/kg. Although ipilimumab is used for the treatment of brain metastases, it paradoxically did not seem to reduce the risk of developing brain metastases.