Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment. Their mechanism of action raises the question of possible exacerbation of preexisting multiple sclerosis (MS). The aim of our study was to assess the risk of increased MS activity, defined by the occurrence of a relapse and/or a new MRI lesion, after ICI initiation. METHODS: This French multicentric study collected retrospective and prospective data on patients with MS treated with ICIs after a cancer diagnosis. RESULTS: We identified 18 patients with a median age of 48 years. Three of them (17%), all aged 50 years or younger, with a relapsing-remitting course, showed clinical and/or radiologic signs of MS activity 3 to 6 months after ICI initiation. They had stopped disease-modifying treatment (DMT) several months earlier, at the time of cancer diagnosis. Only one had both clinical and MRI activity, with mild severity and complete recovery. DISCUSSION: Our study suggests that the overall risk of MS activity under ICI is low and could be mainly driven by DMT discontinuation, as in MS in general. Although larger studies are needed for better risk assessment in younger patients with more active disease, ICI should be considered when needed in patients with MS.

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study.

BACKGROUND: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. OBJECTIVE: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. METHODS: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. RESULTS: Recruitment was stopped prematurely due to slow inclusions (n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) (p = 0.79)). CONCLUSION: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.

History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort.

OBJECTIVE: To evaluate the risk of relapses during pregnancy and in the first 3 months after delivery in 2 successive pregnancies in a cohort of French and Italian women with multiple sclerosis (MS). METHODS: A total of 93 women were included if they had had 2 pregnancies followed prospectively after MS onset between January 1993 and 2013. The association of a relapse during pregnancy or the first postpartum trimester in pregnancy 1 and pregnancy 2 was evaluated by univariate logistic regression. RESULTS: A majority of women did not experience any exacerbation in the 3 months after delivery (31.2% and 23.7%, respectively, relapsed after pregnancy 1 and 2; p = 0.32). A total of 7.6% had a relapse after both pregnancies. The risk of relapse after pregnancy 2 was not associated with the number of relapses in the prepregnancy year (odds ratio [OR] 1.52 [0.57-4.05]) or during pregnancy (OR 1.57 [0.52-4.79]) or with the occurrence of a relapse after pregnancy 1 (OR 0.86 [0.29-2.50]). CONCLUSIONS: Our work provides original data on the evolution of successive pregnancies in MS, showing a similar (and even lower) disease activity in the second pregnancy. There was no correlation of activity in successive pregnancies. Therefore, counseling of women with MS who consider having a second baby should be the same as for the first one.

Role of exclusive chemotherapy as first line treatment in oligodendroglioma.

PURPOSE: The optimal therapy of oligodendrogliomas remains uncertain. Although chemosensitive, these tumors are not chemocurable. We investigated whether chemotherapy delays the need for radiation therapy (RT) without decreasing length and quality of survival. METHODS AND MATERIALS: Among 89 patients treated for oligodendrogliomas at the Centre Léon Bérard of Lyon from 1982 to 1999, 59 patients fitted inclusion criteria, having had centrally reviewed pure oligodendroglioma requiring treatment. According to the WHO's classification 35 patients had Grade III and 24, Grade II oligodendrogliomas. RESULTS: According to the intent to treat, patients were retrospectively classified in three groups as exclusive RT (Group 1), radio-chemotherapy (Group 2), or exclusive chemotherapy (Group 3). Median progression-free survival (PFS): was 47 months [95% confidence interval (CI) 39-56], and median overall survival (OS) was 109 months (95% CI 83-134). In univariate analysis, PFS was correlated with frontal location and WHO classification; OS was correlated with frontal location and Post-operative Karnosky performans status both appearing as independent prognostic factors for OS in multivariate analysis. There was no significant difference between the treatment groups with regard to PFS (P = 0.82) and OS (P = 0.64). In the group of patients treated with exclusive chemotherapy the 5-year PFS and OS rates were 44 and 71%, respectively. CONCLUSION: Front-line exclusive chemotherapy results in prolonged OS in patients with confirmed pure oligodendroglioma. Whether this strategy improves quality of life remains debatable.

Steroid hormones in multiple sclerosis.

The possible influence of steroid hormones in multiple sclerosis (MS) has been a matter of great interest. A first illustration comes from the analyses of the influence of gender on susceptibility to MS and on MS severity. A series of arguments emerge in favour of a possible influence of steroid hormones in MS. The menstrual cycle, and even more pregnancy, may influence the clinical evolution of MS. In the PRIMS study, there was a dramatic decrease in the relapse rate during pregnancy, especially in the third trimester, with a rebound increase in the 3 months post partum. Animal studies have provided further confirmatory results. Many experiments have shown that sex steroids may have immunological effects, in preventing or treating experimental allergic encephalomyelitis. They could also have an effect on myelinating and remyelinating the peripheral and possibly the central nervous system. These clinical and experimental data have led to consider sexual steroids as potential therapeutic tools for preventing relapses in women with MS, in particular in the post-partum period.

[Cytoimmunological profile of cerebrospinal fluid in diagnosis of multiple sclerosis]. / Le profil cytoimmunologique du LCR lors du diagnostic précoce de la sclérose en plaques.

The purpose of this paper is to report cerebrospinal fluid (CSF) findings in multiple sclerosis (MS) from our laboratory, to discuss the implications of CSF abnormalities in terms of diagnosis. Paired CSF-serum samples from of 1533 on 3893 patients with suspected neurological diseases over a 10 year period were analysed by routine laboratory microscopy and assays of immunoglobulin G by isoelectric focusing for the detection of intrathecal oligoclonal IgG. Patients were grouped further into four headings according to their disorders: MS (625 cases), definite (246 cases) probable (123 cases) and possible (256 cases) according to Poser, others inflammatory neurological diseases (91 cases), various non-inflammatory neurological disorders (732 cases) and uncertain neurological disorders (85 cases). Definite MS group (16%) was compared to non-inflammatory neurological disorders (48%). Important signs for activity of multiple sclerosis are observed. Cell counts were 10/microl in 71% (N < or =2/microl). Inflammatory cytology is observed after concentration and cytocentrifugation on slides with activated B-lymphocytes, lymphoplasmocytes and/or plasmocytes (76%), total protein concentration is increased in 37% (N < 0.40g/l), CSF/serum albumin quotient with age dependent references for the blood-CSF barrier dysfunction is increased in 26% (N < 0.65 x 10(-2)), IgG index for intrathecal synthesis of IgG is increased in 69% (N < 0.70), sensitive detection of oligoclonal IgG restricted to CSF by isoelectric focusing is positive in 91% (86-96%) with a specificity of 96% (93-99%).