Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment.

Published on Apr 1, 2021in Multiple sclerosis and related disorders2.889
· DOI :10.1016/J.MSARD.2021.102747
Sources
Abstract
Abstract Background Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). Objective : Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. Methods We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30th 2020. Results Eight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression. Conclusion A relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.
References28
Newest
#1Ralf Gold (RUB: Ruhr University Bochum)H-Index: 86
#2Douglas L. Arnold (Montreal Neurological Institute and Hospital)H-Index: 111
Last. Catherine Miller (Biogen Idec)H-Index: 6
view all 8 authors...
Introduction:We report safety and efficacy in patients treated with dimethyl fumarate (DMF) for ~9 years in ENDORSE. Lymphocyte analysis data are also reported.Methods:Incidence of serious adverse ...
18 CitationsSource
BACKGROUND: Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population. OBJECTIVE: To evaluate DMF tolerability, safety and persistence in MS in a real-world setting. METHODS: We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect da...
11 CitationsSource
#1Esther Melamed (University of Texas at Austin)H-Index: 9
#2Michael William Lee (University of Texas at Austin)H-Index: 1
Over the past two decades, the field of multiple sclerosis (MS) has been transformed by the rapidly expanding arsenal of new disease modifying therapies (DMTs). Current DMTs for MS aim to modulate innate and adaptive immune responses toward a less inflammatory phenotype. Since the immune system is also critical for identifying and eliminating malignant cells, immunosuppression from DMTs may predictably increase the risk of cancer development in MS patients. Compared with healthy controls, patien...
10 CitationsSource
#1Elaine Kingwell (UBC: University of British Columbia)H-Index: 25
#2Feng Zhu (UBC: University of British Columbia)H-Index: 20
Last. Helen Tremlett (UBC: University of British Columbia)H-Index: 53
view all 6 authors...
BACKGROUND: Lifespan is 6-10 years shorter in multiple sclerosis (MS), but the reasons remain unclear. Using linked clinical- and population-based administrative health databases, we compared cause-specific mortality in an MS cohort to the general population. METHODS: MS patients in British Columbia (BC), Canada, were followed from the later of first MS clinic visit or January 1, 1986, to the earlier of death, emigration, or December 31, 2013. Comprehensive mortality information was obtained by ...
6 CitationsSource
#1Nina Grytten (Haukeland University Hospital)H-Index: 16
#2Kjell-Morten Myhr (Haukeland University Hospital)H-Index: 65
Last. Øivind Torkildsen (Haukeland University Hospital)H-Index: 28
view all 10 authors...
Background:Risk of cancer in multiple sclerosis (MS) patients compared to their siblings is unknown.Objective:The objective was to prospectively investigate the risk of cancer among MS patients com...
12 CitationsSource
#1Nathaniel Edward Bennett Saidu (Paris V: Paris Descartes University)H-Index: 13
#2Niloufar Kavian (HKU: University of Hong Kong)H-Index: 19
Last. Jérôme Alexandre (Paris V: Paris Descartes University)H-Index: 35
view all 7 authors...
Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). It induces protein succination leading to inactivation of cysteine-rich proteins. It was first shown to possess cytoprotective and antioxidant effects in noncancer models, which appeared related to the induction of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) pathway. DMF also displays antitumor activity in several cellular and mice models. Recently, we...
38 CitationsSource
#1Emanuele D’Amico (University of Catania)H-Index: 19
#2Clara Grazia Chisari (University of Catania)H-Index: 9
Last. Francesco Patti (University of Catania)H-Index: 59
view all 11 authors...
Introduction. The complexity of understanding cancer risk in MS is increased by inconsistencies in study design, and the lack of age-, sex-, and ethnicity-specific risk estimates. Aims of our study were to estimate the incidence of cancers in the MS population of Catania (Italy) and to evaluate the impact of disease-modifying treatments (DMTs) in cancer risk. Materials and Methods. We screened 2,730 PwMS according to the MS criteria of Mc Donald 2010 referring to MS Centre of Catania in the peri...
11 CitationsSource
#1Shabana Naz (Ayub Medical College)H-Index: 1
#2Abdur Rehman (Ayub Medical College)H-Index: 3
Last. Touqeer IqbalH-Index: 1
view all 6 authors...
Background: Abnormal uterine bleeding is a common problem encountered by the gynaecologists, leiomyoma being one of the most common causes. An accurate knowledge of the different variants and secondary changes occurring in leiomyoma is essential as some of these may mimic malignancy clinically, radiologically and histologically. Some important examples being atypical, cellular and mitotically active leiomyoma. Similarly, hydropic and myxoid change can be misdiagnosed as malignancy. While dealing...
4 Citations
#1Matthew Dodson (UA: University of Arizona)H-Index: 18
#2Montserrat Rojo de la Vega (UA: University of Arizona)H-Index: 19
Last. Donna D. Zhang (UA: University of Arizona)H-Index: 71
view all 6 authors...
The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cas...
100 CitationsSource
In the 1990s, the first disease-modifying therapies (DMTs) for multiple sclerosis (MS) were injectable immunomodulatory (IM) drugs, including four different interferon-β preparations and glatiramer acetate. Since 2000, more than 15 immunosuppressant (IS) drugs have been used, with a more or less specific action on inflammation. These include monoclonal antibodies targeting CTL4, the integrin receptor, the interleukin (IL)-2 receptor, CD19, CD20, CD52, and the sphingosine 1 phosphate family. The ...
38 CitationsSource
Cited By0
Newest