D'Sa is a consultant hematologist and clinical lead for the University College London Hospital (UCLH) Centre for Waldenström’s Macroglobulinemia and Associated Disorders, as well as an honorary associate professor at the UCL Cancer Institute. She also serves as the hematological lead in the joint neurohematology service at the National Hospital for Neurology, Queen Square, London.

Dr. Shirley D'Sa 

Dr. Shirley D'Sa discusses the importance of catching peripheral neuropathy in patients with Waldenstrom macroglobulinemia early on, and how to treat it.

Mitigating Peripheral Neuropathy During Cancer Treatment

Waldenstrom macroglobulinemia, also referred to as WM, is a type of blood cancer classified under non-Hodgkin's lymphoma, and is also sometimes called lymphoplasmacytic lymphoma, according to the Mayo Clinic website.

Waldenstrom macroglobulinemia begins in the white blood cells, and following these changes in the cells, can turn into cancer which can build up in the spongy material inside of bones where blood cells are made (bone marrow), crowding out healthy cells. There are various treatment approaches that are optimal for patients within this population, including chemotherapy, targeted therapy and even watchful waiting, the Mayo Clinic website explains. However, one important side effect of some WM treatment approaches is peripheral neuropathy.

Peripheral neuropathy can occur when the nerves that are located outside of the brain and spinal cord are damaged from treatment, causing weakness, numbness and pain, specifically in the hands and feet, though it can also affect other areas and body functions.

In an interview with CURE, Dr. Shirley D'Sa sat down to discuss the importance of catching peripheral neuropathy in patients with WM early on, and how to treat it.

Peripheral neuropathy is common in people with WM, but one has to remember that peripheral neuropathy is also prevalent in the general population. There are hundreds of causes of neuropathy. Some are more common than others, such as diabetes, and frankly, things like excessive alcohol consumption can damage nerves. Anything toxic to nerves over a long period can cause problems. So, we always consider this background when we assess a patient. We don't want to instantly attribute it to WM, because often, it's not the WM causing the problem.

Our approach involves a joint clinic where we see patients together. We bring our respective viewpoints from neurology and hematology. The patient's history is paramount—taking a detailed account of their neuropathy experience. How quickly did it develop? What makes it worse? What makes it better? What is the distribution? Is it mainly in the hands or feet? Do they have other symptoms? Do they have balance problems? Do they have autonomic symptoms, which relate to the autonomic nervous system that regulates blood pressure and appetite? A detailed history is crucial, followed by a clinical examination, particularly of the nervous system.

My colleague conducts this in a very systematic and recorded manner. We then follow up with additional tests, such as imaging scans like MRI, and inflammatory nerve antibody testing. The most common antibody is against myelin-associated glycoprotein. Sometimes IgM antibodies have this property. We sequentially consider the possible causes, and occasionally, we biopsy a nerve if necessary. There's quite a range of possibilities, and only if we feel there is as firm a connection to WM as we can prove, and the patient has progressive symptoms, do we consider offering or recommending treatment.

Ultimately, the treatment involves addressing the underlying WM, because the WM cells are responsible, indirectly via mechanisms like antibody production, or occasionally by directly invading nervous tissue. So, it's really about very clear diagnostics, consistent testing, a careful analysis of causality, and also establishing very good, clear guidelines for each patient.

What are we trying to achieve in that patient? If they have progressive disability, for example, then it's almost an emergency to get them treated. If it's mainly sensory symptoms like pain and loss of temperature, they are less likely to respond well to treatment, and we will then address that with symptomatic measures such as special pain-relieving medication, given in a supervised manner.

People do worry if pain medication might mask anything, but the answer is no. It is important to monitor the rate of change, so we do keep people under follow-up. If people have what we believe is a WM or IgM-related neuropathy, then we will consider treatment with rituximab, chemotherapy plus rituximab, or BTK inhibitors, for example. This is not done sequentially but based as far as we can on guidance.

There are some pretty up-to-date guidance documents coming out from the recent international workshop, and one will be on peripheral neuropathy. So, I hope this is helpful for a professional audience, but it's worth pointing that out to your caregiver or doctor if you encounter this, because it's something that many doctors find quite challenging to manage neuropathy, as it's a tricky subject, and hematologists are not neurologists.

Close collaboration is essential. The other thing to remember is that if people are facing problems with their functionality, there are many ways to adapt. There are aids to help you handle things, pick things up, prevent foot drop, etc. So, ideally, there should be a comprehensive strategy to treat these patients.

Transcript has been edited for clarity and conciseness.

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Dr. Shirley D'Sa

Mitigating Peripheral Neuropathy During Cancer Treatment

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