Multiple Sclerosis and Cancer: A Devastating Comorbidity
Chronic illnesses affect millions of people worldwide, including both autoimmune and genetic diseases, which deteriorate the body's cellular function and integrity.
Multiple sclerosis (MS) and cancer are two of the most common autoimmune and genetic diseases, respectively. Managing MS requires a structured treatment plan relying heavily on the immune system, but altering it can be counterproductive once cancer comes into the picture.
MS and your immune system
The immune system acts as a protective measure toward potential threats. It fights diseases, facilitates healthy cellular function and keeps the body in homeostasis, giving it stability. Sometimes, this system malfunctions, leading to conditions such as multiple sclerosis and cancer.
"It's possible that the immune system could play a positive role for MS and cancer in terms of immunosurveillance," said Robert Watson, M.D., from Florida State University. "They're still working out what the relationship is, especially since immunotherapy has become available to treat MS."
Multiple sclerosis occurs when the immune system mistakes myelin—the protective sheath surrounding nerves made up of proteins and phospholipids, which allows for ample electrical impulse transmission—as a threat. This breakdown happens in the central nervous system (CNS), which is made up of the brain and spinal cord, and subsequently leads to permanent physical and neurological damage.
'The problem with MS is that the immune system is overreacting.'
"The immune system is pretty good at multitasking," said Michael Kornberg, M.D. and Ph.D. from Johns Hopkins University. "The problem with MS is that the immune system is overreacting."
Cancer is brought on by a similar immune false alarm originating in genetics. For various reasons, including environmental causes, genes can mutate, adversely affecting normal cell operation. This can result in unchecked cell division and growth. Typically, a normally functioning immune system promotes regeneration of healthy cells and the death of abnormal or unhealthy cells. With cancer, there is a complete system breakdown in which unhealthy cells can multiply, spread and bypass immune system regulations.
"The goal with immunotherapy with cancer is to make it overactive," Kornberg continued. "Since we've never actually seen that clinically, the two conditions seem to work independently from each other."
When cancer appears
A large study out of Norway indicated that people with MS have a 12 percent to 14 percent higher risk of cancer overall, with some significant jumps for specific cancers. However, it's unclear if this is due to the nature of MS, the disease-modifying therapies (DMTs) used to treat it, or a combination of both." The caveat is that studies that have shown the possible increased risk weren't sure whether it was a normal chance or that one caused the other or, statistically, that they both happened to occur in the same patient," Watson said. "The ones they seem pretty confident on are bladder cancer and cancers in the central nervous system."
He surmised bladder cancers likely occur because a lot of MS patients have indwelling catheters susceptible to infections. Recurrent infections can in turn lead to chronically inflamed bladder cells, which can mutate into abnormal cells over time.
"Because of biological mechanisms there's no innate risk of developing cancer with MS," Kornberg said. "I don't think there's an association outside of treatments and meds." Kornberg used Cladribine and Ocrelizumab as examples of MS medications linked to an elevated risk of certain types of cancer.
With multiple sclerosis, DMTs pose a risk of suppressing the body's natural defense mechanisms against cancer.
Bob Shankle, a Florida resident who has had MS for 25 years and is in remission from blastic plasmacytoid dendritic cell neoplasm (BPDCN), began his MS with a limp and some visual disturbances, and has since lost mobility.
"When it first started, I could work with it, but I had to quit because of my leg disability," Shankle reported. "It was all on my left side—I was weak, but I didn't have any spasms."
His cancer appeared six years ago, and Shankle spent 25 weeks in and out of the hospital for treatment. He had several bone marrow biopsies and countless intravenous treatments, but was miraculously cured with an experimental drug called SL-401, which was later approved by the FDA.
"It was hard to find a treatment to treat MS without making the cancer worse," Shankle said.
This is a struggle for anyone trying to treat comorbidities. With multiple sclerosis, DMTs pose a risk of suppressing the body's natural defense mechanisms against cancer.
"For example, if you have chronic inflammation and you use DMTs, it could activate the immune system to attack the tumors," Watson said. From there, it's a matter of finding the right balance to moderate both conditions.
"The one that is seen the most often is people who make antibodies against their tumor, but the antibodies also have to attack parts of their nervous system," Watson continued. "So, the immune system is working hard to fight the tumor, but allows for an attack of the CNS."
Kornberg also emphasized the moderating factor of fragility on this comorbidity.
"Fragility is a negative diagnostic indicator, including for cancer," he said. "The type of cancer outcome is not dependent on MS unless they have severe frailty or disability."
Working out is essential
The meta-analysis of how cancer and MS treatments interact is still fresh. There is much research to be done to develop an understanding of their interaction, which can then provide better treatment options for patients and caregivers, and pave the way for further studies.
"I was put on a lot of different pills, but none of them worked," Shankle said. "Steroids have been the most helpful, but I also take medication for pain and to help me sleep."
Mobility impairments and restlessness are common symptoms of both MS and certain types of cancer. Shankle strongly emphasized the importance of physical activity.
"If you're weak, you have to work out or you'll become a vegetable—it keeps me going," Shankle said. "Just don't overdo it, because your body can't heal quickly." Frequent visits from an occupational therapist are another crucial part of both cancer and MS treatment regimens.
'The overarching message is that cancer is not innately more common with the MS population, but certain therapies can increase the risk.'
Watson emphasized the importance of lifestyle and regular doctor visits.
"If I were a primary care physician I would look very carefully for abnormalities in the blood and urine," Watson said. "Patients with MS should avoid things that cause the risk of cancer, but really stay on top of CTs of the chest if they smoke." However, both Watson and Kornberg stressed the necessity for smoking cessation with MS patients.
"The overarching message is that cancer is not innately more common with the MS population, but certain therapies can increase the risk," Kornberg said. "Getting the recommended age-appropriate scans and cancer screenings is the best way to moderate it."
