Treating Von Hippel-Lindau (VHL) disease
- Von Hippel-Lindau (VHL) disease is a condition that can cause one or many tumors or cysts to form in various places throughout the body including the brain/spine, eyes, adrenal glands, kidneys, pancreas, inner ear, and reproductive organs.
- VHL does not yet have a cure. Goals of treatment are to closely monitor patients for tumors and cysts so doctors can take note of the ones that are going to become a problem and either remove them or start medication to suppress them.
- A newer option for VHL treatment came last summer in the form of the FDA-approved drug belzutifan. Despite there being “a lot of unanswered questions” with this drug, one of our experts consider it to be a “wonderful alternative.”
There are no universal recommendations for Von Hippel Lindau’s treatment. That being said, there is much to consider when thinking about treatment for this lifelong disease.
Learning about Von Hippel-Lindau DiseaseRead More
- People who have a parent with VHL have a 50 percent chance of inheriting the disease.
- Not all people who develop the disease have it in the family. That means that the person has developed a de novo mutation – a genetic alteration that is present for the first time in one family member.
- VHL can cause cysts or tumors (both cancerous and noncancerous) based in the blood vessels in many different parts of the body.
- Each person with VHL can have very different symptoms and manifestations of the disease.
- Signs of the disease vary greatly depending on how many tumor(s) arise – there can be any number – and where those tumors are located.
- VHL isn’t considered cancer, but it can contribute to cancer formation.
Von Hippel-Lindau disease symptoms
VHL can cause any number of tumors and cysts, which can be cancerous or benign (noncancerous). These tumors and cysts can be found in:
- The brain/spine
- The eyes
- The adrenal glands
- The kidneys
- The pancreas
- The inner ear
- The reproductive organs
Below are some of the signs of the disease that can occur when tumors and cysts (both cancerous and noncancerous) form in different parts of the body. But, it’s important to note that these symptoms will vary according to the location and size of the tumor.
- Blindness from tumors in the retina of the eye.
- Balance issues and weaknesses of different parts of the body from tumors in the brain.
- Impaired hearing or balance issues from tumors of the inner ear called endolymphatic sac tumors (ELST).
- High blood pressure, episodes of racing heartbeat, palpitations, nausea, headaches, vision changes, sweating, and turning pale from pheochromocytoma tumors of the adrenal gland.
- Blood in the urine (hematuria) from cancerous kidney tumors (renal cell carcinoma).
- Problems with vision.
How is Von Hippel-Lindau’s (VHL) disease diagnosed?
The most conclusive way to get a VHL disease diagnosis involves genetic testing to look for the mutated gene. Eligibility criteria to be considered for this kind of test mostly include those with a family history of VHL and those who experience multiple tumors in certain organs. More details about these parameters can be found here.
Does VHL have a cure?
VHL does not yet have a cure. The goals of treatment are to closely monitor patients for tumors and cysts so doctors can take note of the ones that are going to become a problem and either remove them or start the medication to suppress them.
Dr. Craig Rogers, Chair of Urology, Henry Ford Health, and head of Von Hippel-Lindau Clinical Care Center told SurvivorNet that many patients with the disease lead full lives.
“There are plenty of patients that do that now because of close monitoring, picking it up early, medications. Some patients live a very long time with this,” he explained.
VHL disease treatment options
Treatment options vary greatly because of the wide range of possible manifestations of the disease, and a treatment path can only be determined after careful evaluation of each person’s situation in its entirety. Some patients may have one tumor that needs to be removed immediately; some patients may have multiple tumors with one in need of immediate attention, and others may simply have cysts or tumors that just need to be monitored.
Mainly, treatment for VHL revolves around finding and removing tumors as soon as possible to prevent them from affecting your health or causing any further damage. Your doctor will determine the appropriate method for eliminating these tumors by:
- Medication (like belzutifan)
- Radiofrequency ablation
- Targeted therapy
- Applying extreme cold (cryotherapy)
When a patient with an official or suspected VHL diagnosis sees Dr. Rogers, his initial steps are as follows:
- Make sure the patient has gone through all the necessary screening practices like blood work and imaging to properly assess the situation and make sure they’re aware of every tumor and cyst currently present.
- Coordinate care so that the patient can see a specialist for each of their affected areas (if there are multiple).
- Decide if surgical removal or a wait and watch approach is necessary for any current manifestations.
- Plan on what happens next. “So, there is an order,” Dr. Rogers said. “We all get together, and we decide, does it need to be treated? What needs to be treated first? And then how are we gonna follow them?”
If a VHL patient has kidney tumors, there is a more “well-defined” protocol to follow, according to Dr. Tobias Else, an endocrinologist who leads the Comprehensive Clinical Care Center for Von Hippel-Lindau disease at the University of Michigan Health Rogel Cancer Center.
“There can be cysts in the kidney as well – we don’t really care much about those – we look at the solid tumors, which are renal cell cancer,” Dr. Else explained. “We tend to watch them until they approach the size of three centimeters. And that’s when our [urologic] oncologist will do the surgery to remove those tumors and then sometimes they remove other ones as well, but very often the patient then comes back to us for further surveillance.”
Overall, each case is different and may walk the fine line between waiting and watching and surgical removal. That’s why both Dr. Else and Dr. Rogers recommend an interdisciplinary team for VHL patients with all the necessary specialists for your case.
“What’s most important is that you have somebody who actually oversees this for each patient,” Dr. Else said. “I always tell my patients my role is pretty small and just keeping everything together and that you’re up to date on imaging and surveillance.”
Von Hippel-Lindau treatment — Belzutifan
The newest option for VHL treatment came on August 13th, 2021, in the form of the FDA-approved drug belzutifan. Despite “a lot of unanswered questions” with this drug, one of our experts considers it a “wonderful alternative.”
Welireg (Belzutifan) is the first prescribed medication for Von Hippel-Lindau treatment. It’s available for adults who suffer from VHL-associated kidney cancers or tumors in (the brain, spine, or pancreas). The approval came after a small clinical trial on 61 VHL patients with associated tumors who took 120 mg of belzutifan daily for 18 months. The reported results showed incredible results where half of the participants had tumor shrinkage of 30% and experienced only mild side effects.
Belzutifan is specific for patients who require treatment but don’t need immediate surgery. Belzutifan works by blocking a certain pathway that can influence cells to grow abnormally, named ‘hypoxia-inducible factor-2 alpha or HIF-2α’. By successfully blocking this pathway, the blood supply necessary for tumors to grow is cut off, so they shrink.
Belzutifan side effects
- Low oxygen saturation in the blood.
- A decrease in hemoglobin – a protein in your red blood cells that carries oxygen to your body’s organs and tissues and transports carbon dioxide from your organs and tissues back to your lungs.
- Lower than normal hemoglobin levels = a low red blood cell count (anemia).
- Increased creatinine
- Increased glucose levels
“Occasionally, patients will need transfusions or other treatments for the anemia for the low red blood cell count,” Dr. Else said of treating the side effects of belzutifan. “Or they might experience some, you know, tiredness, fatigue, sometimes shortness of breath, but usually that actually becomes better once they’re on the drug for three or four months, and then it kind of levels out at a new normal, and a lot of patients will have no severe ongoing side effects from that drug.”
Issues and precautions to consider with Belzutifan treatment
Dr. Else says this drug is probably not the best choice for everyone. Below are some considerations:
- Anemia concerns: “A patient with baseline anemia… we’d probably not necessarily treat them with a drug that leads to further critical reduction of those levels,” Dr. Else said.
- Fertility concerns: “We don’t know what the effects on fertility of this drug is,” Dr. Else said. “We also know that it’s not compatible with pregnancy at all… You cannot be pregnant with this drug; it will lead to an abortion.”
- We don’t know the long-term effects: “We don’t know whether there is something that we just discover in 10 years that is irreversible,” Dr. Else explained. “And because we have usually good therapies otherwise, I think that’s something which patients just simply need to know about.”
- It’s unclear if VHL-related tumors will eventually stop responding to belzutifan: “So we know how the tumors react in two years, three years, four years,” Dr. Else said. “But we don’t know whether, after six, seven years of treatments the patient or the tumor might not actually respond to belzutifan anymore and might become actually even more difficult to treat.”
- Potential impacts of monitoring kidney tumors: When monitoring renal cell carcinoma of the kidney, doctors generally consider 3cm to be a “cut-off” for a size that would generally necessitate surgical removal. “That cut-off… is that the same for tumors you’re treating with belzutifan? We just simply don’t know,” Dr. Else said.
Please check the leaflet for more information about belzutifan indications and usage.
“I think the opportunity that we can treat patients with VHL-related tumors with other means than surgery is probably one of the greatest things that I’ve experienced during my professional life working with patients with VHL,” he said. “It needs an experienced physician to discuss the concerns around those drugs [as well as] the unknown with the patient.”
“And, as always, I think patients are the leaders in this game … This is something which they make the decisions [about].”
Nevertheless, there’s a crucial need for further investigations through future trials on the long-term efficacy and safety of belzutifan — there’s a lot we don’t know yet.
Questions to ask your doctor
- What are the potential treatment paths for me with my specific case of VHL?
- Which doctors will be on my “team” to help treat and manage my VHL?
- Is taking the drug belzutifan an option for me?
- What to expect with VHL?
- What can you do to improve your quality of life with VHL?
The Bottom Line
Von Hippel-Lindau’s treatment can vary from patient to patient depending on the type, location, and stage of the disease. Your chances of fighting off this disease are higher when caught early.
Belzutifan is a new promising candidate for treating many VHL-associated tumors, but there’s a lot that we don’t know about its prolonged use.
If you have a family history of VHL, we recommend that you get tested for the VHL gene mutation so that you can stay ahead of this disease. On the other hand, if you have VHL and are planning to have a baby or start a family, you should think about consulting with a genetic counselor first.
Since living with VHL is very challenging, especially ‘the not knowing part’ whether you’ll develop cancer or not, you should be wise to follow up regularly with your doctor on your condition.