Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society.

BACKGROUND: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk. OBJECTIVE: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS). METHODS: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal. RESULTS: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations. CONCLUSION: These recommendations propose a strategic approach to managing cancer risk in PwMS.

Evidence of disease activity during pregnancy and post-partum in MS patients treated with high-efficacy therapies.

BACKGROUND: Multiple sclerosis (MS) predominantly affects women of childbearing age. Due to the risk of teratogenicity, women with active multiple sclerosis (MS) who require high-efficacy therapies (HET) may need to discontinue treatment during pregnancy. Fingolimod and Natalizumab withdrawal increases the risk of disease reactivation, a risk not commonly associated with anti-CD20 therapies. However, comparative data are limited during pregnancy and post-partum. Our aim was to compare evidence of disease activity during pregnancy and post-partum in women treated with HET (anti-CD20 therapies, Natalizumab or Fingolimod) before conception, whether or not exposed during pregnancy. METHODS: In this single-center retrospective study, we included consecutive pregnancies of relapsing-remitting MS patients and classified them in three groups according to the last HET used before conception: « anti-CD20 ¼ « Natalizumab (NTZ) ¼ and « Fingolimod (FGD) ¼. The main outcome was annualized relapse rate (ARR) during pregnancy and post-partum. RESULTS: We included 66 pregnancies: 21, 24 and 21 in anti-CD20, NTZ and FGD groups respectively. Overall, mean ARR (SD) increased from 0.36 (0.6) during the preconception year to 0.60 (1.3) during pregnancy and to 1.03 (2.0) in the first 3 months post-partum. Mean ARR in anti-CD20 group (0.09 (0.3)) during pregnancy and the first 3 months post-partum was lower compared with NTZ (0.48 (0.6); p = 0,09) and FGD (1.50 (1.8); p = 0.001) groups. Proportion of pregnancies with radiological activity during pregnancy and post-partum in anti-CD20 group (5.2 %) was lower compared with NTZ (63.1 %; p < 0.001) and FGD (72.2 %; p < 0.001) groups. There was no significant difference in the evolution of EDSS score from conception to post-partum between each group (p = 0.75). CONCLUSION: Evidence of disease activity was significantly lower in patients exposed to anti-CD20 therapies before conception. This study suggests that use of anti-CD20 therapies is an efficient option to prevent disease reactivation during pregnancy and post-partum.

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.