Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas.

Trichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. "AcSé Nivolumab" is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The primary endpoint 12-week objective response rate was 9.1% (N = 1/11) with 1 partial response. Six patients who progressed under previous lines of treatment showed stable disease at 12 weeks, reflecting a good control of the disease with nivolumab. Furthermore, 54.5% of the patients (N = 6/11) had their disease under control at 6 months. The 1-year overall survival was 80%, and the median progression-free survival was 8.4 months (95%CI, 5.7 to NA). With 2 responders (2 complete responses), the best response rate to nivolumab at any time was 18.2% (95%CI, 2.3-51.8%). No new safety signals were identified, and adverse events observed herein were previously described and well known with nivolumab monotherapy. These results are promising, suggesting that nivolumab might be an option for patients with advanced trichoblastic carcinomas. Further studies on larger cohorts are necessary to confirm these results and define the role of nivolumab in the treatment of trichoblastic carcinomas.

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.

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.

[Idiopathic granulomatous mastitis associated with erythema nodosum]. / Mastite granulomateuse idiopathique associée à un érythème noueux.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare, chronic, granulomatous, inflammatory disorder with potentially misleading clinical and radiological features. IGM is diagnosed after exclusion of infectious or tumoral diseases. Herein we report a case of erythema nodosum associated with IGM, which serves as a reminder that erythema nodosum may constitute an extra-mammary sign of IGM. PATIENTS AND METHODS: A 36-year-old nulliparous woman presented with fever and skin rash at our dermatology clinic at the North Franche-Comté hospital in July 2017. Symptoms had occurred 2 days previously. The patient had a fever of 38.8°C and typical erythema nodosum on the limbs. Physical examination showed an irregular, inflammatory, abscessed mass measuring 20cm with multiple shrinkage zones that had been developing for 4 weeks and for which breast examinations were being performed. Laboratory tests showed an inflammatory state (CRP 155mg/mL, WBC 14.6×109/L), other tests (serum electrolytes and calcium, hepatic and renal tests, Streptotest, T-spot, HIV, HBV, HCV serology, anti-streptolysin, anti-streptodornase, local microbiology samples, antinuclear antibodies, soluble antigens antibodies, hemocultures, angiotensin-converting-enzyme and chest x-rays) were normal. Microbiology investigations were negative. Mammography revealed invasive mastitis. Breast sample biopsies showed giant cell granulomas without caseous necrosis or tumor cells, and histochemical staining (PAS, Ziehl, Grocott, Gram) was negative. The final diagnosis was of IGM associated with erythema nodosum. Symptoms rapidly improved with oral steroids. DISCUSSION: As reported herein, erythema nodosum may be associated with IGM and support the diagnosis thereof. This association is rare, with fewer than 30 case reports described in the literature. IGM is an uncommon benign disorder of the breast that can mimic two frequent breast disorders: breast carcinoma and breast abscess. It usually occurs in young sexually active women. It appears as a tumor with an inflammatory solid painful mass, with nipple and skin retraction, occasionally with abscesses and accompanied by homolateral axillary lymphadenopathies. Radiologic findings are usually not specific for or suggestive of cancer. The histopathological picture of IGM is characterized by the presence of multinucleated giant cells and epithelioid histiocytes forming non-caseating granulomas around lobules. Minor ductal and periductal inflammation is usually present. IGM is rarely associated with autoimmune system manifestations, especially erythema nodosum, arthritis, episcleritis or hidradenitis suppurativa. Although the physiopathology of IGM remains unclear, this case serves as additional evidence that the etiology of IGM is of autoimmune origin. While there is no recommendation for the treatment of IGM, oral steroids remain the cornerstone of therapy. CONCLUSION: We report a case of IGM associated with erythema nodosum. Dermatologists must be aware of this association.

[Acquired C1 esterase inhibitor deficiency via bradykinin-mediated angioedema: Four cases]. / Angiœdème bradykinique par déficit en C1 Inhibiteur acquis : quatre cas.

BACKGROUND: Acquired C1-esterase inhibitor (C1-INH) deficiency angioedema (C1-INH-AAE) is a form of bradykinin-mediated angioedema. This rare disorder is due to acquired consumption of C1-INH, hyperactivation of the classic pathway of human complement, and potentially fatal recurrent angioedema symptoms. Clinical symptoms of C1-INH-AAE are very similar to those of hereditary angioedema (HAE) but usually appear after the fourth decade of life and induce abdominal pain less frequently. Laboratory tests are essential in establishing the diagnosis with low levels or abnormal structure and function of C1-INH. Most patients present C1-INH autoantibodies. Furthermore, C1q is reduced in AAE, contrary to HAE. The long-term prognosis is determined by associated hematologic malignancies. PATIENTS AND METHODS: We report 4 cases of C1-INH-AAE associated with lymphoproliferative disorders referred to the Reference Centre for Angioedema of Besançon, France. The patients were aged between 60 and 77 years. C1 INH antibodies were found in three patients. Symptoms were triggered by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) in 3 patients. Hematologic malignancy was present at diagnosis (one case of chronic lymphoid leukemia) or was diagnosed during follow-up (one case of indolent marginal zone non-Hodgkin lymphoma and two cases of monoclonal gammopathy). DISCUSSION: C1-INH-AAE induced by ACE inhibitors or ARBs may be associated with hematologic malignancies. This form of revelation does not necessarily indicate a diagnosis of ACE or ARBs angioedema, and screening should therefore be performed for C1 Inh and C1q. An underlying hematologic malignancy should be routinely sought and the long-term prognosis determined.