[00:01]
Joy Ho: Hi, my name is Joy Ho. I am a haematologist from Royal Prince Alfred Hospital, and I’m delighted that Myeloma Australia has asked me to give a presentation on myeloma side effects and strategies to improve quality of life. These are very important aspects of myeloma care that can sometimes receive less attention while we focus on the effectiveness of treatment. My role today is to address these issues to help patients, nurses and doctors focus on the importance of quality of life.
[00:53]
I am presenting this talk in close collaboration with, and with the fantastic assistance of, Professor Tracy King, our myeloma clinical nurse consultant. I would also like to thank Professor King for supporting this talk with some of her slides.
[01:16]
Let’s first look at how myeloma affects individuals, who may experience different manifestations of the disease. The main disease manifestations are summarised using the CRAB mnemonic, which is commonly used when diagnosing active myeloma. These categories explain some of the ways symptoms and signs can occur in people with myeloma.
[01:58]
Other important features include spinal cord compression caused by the impact of myeloma on the spine, recurrent infections and hyperviscosity symptoms. Hyperviscosity can occur because myeloma produces a paraprotein that can make the blood very thick, sometimes leading to symptoms such as confusion or reduced consciousness.
[02:31]
It is also important to remember that other diagnoses can cause high calcium, renal impairment, anaemia and bone pain. Doctors therefore need to keep an open mind when considering the causes of these symptoms and signs.
[03:00]
When considering quality of life, one of the key issues is balancing the effectiveness of treatment with its side effects. Treatments can cause a range of side effects that are often predictable and manageable. They vary in intensity and duration and may be cumulative. Understanding the possible side effects of treatment can help patients manage and cope with them more effectively.
[03:39]
It can also be helpful to have someone accompany you on the myeloma journey and discuss symptoms with you and your doctors. Patients often try their best to cope with treatment and may under-report their symptoms, so a carer can act as a truth-teller. Reporting issues promptly can help patients remain adherent to treatment and tolerate it better.
[04:27]
In addition to age and other comorbidities, several factors can influence the severity of side effects. These include the number of previous lines of treatment, the length of time a patient has received treatment and whether drugs are used in combination or as a single agent. Toxicities can be particularly significant during the first two or three cycles and may later become milder and more tolerable. Side effects from previous therapies may also compound the effects of current treatment. Performance status, which describes how well a person is functioning overall, is also related to frailty and disability.
[05:42]
I will now look at some of the most common myeloma drugs and explain their common side effects. Bortezomib is a proteasome inhibitor that is given once or twice a week, although it is now usually given weekly. It is often given with dexamethasone and an antiviral such as valaciclovir or aciclovir because it increases the risk of shingles.
[06:21]
Important side effects of bortezomib include peripheral neuropathy, which may require dose adjustments, reduced blood counts and diarrhoea or constipation, which can sometimes alternate.
[06:44]
Lenalidomide is a widely used immunomodulatory drug taken as a tablet. To improve quality of life, patients are often advised to take it at bedtime because this can reduce the impact of the drowsiness associated with treatment. Lenalidomide can also increase the risk of thrombosis or clotting, so patients may be prescribed aspirin or, if they have a higher risk of clotting, a specific anticoagulant.
[07:30]
Resprim may be used to prevent a particular type of pneumonia called Pneumocystis pneumonia. Other possible side effects of lenalidomide include a rash, which often occurs near the start of treatment, reduced blood counts associated with infection, an increased risk of blood clots, fatigue and chronic diarrhoea. Peripheral neuropathy is less common with lenalidomide than with bortezomib.
[08:20]
Pomalidomide is related to lenalidomide and is also taken as a tablet, often at bedtime. It has similar considerations regarding blood thinning and many similar side effects, although it may be used with different treatment partners.
[08:53]
Peripheral neuropathy is a very important side effect because it can significantly affect quality of life. It involves damage, inflammation or degeneration of the peripheral nerves. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system includes the nerves that extend from the spinal cord and supply the rest of the body.
[09:27]
Damage or inflammation of these nerves can change how we feel, move or function. Neuropathy may be sensory, affecting feeling; motor, affecting movement; or autonomic, affecting bodily functions. Autonomic neuropathy may cause changes in blood pressure and can be significant when it is severe.
[10:07]
Sensory neuropathy often begins in the fingertips and toes on both sides and may worsen if it is not managed properly. Treatments particularly associated with peripheral neuropathy include bortezomib and thalidomide. Other drugs in the same groups, such as carfilzomib and lenalidomide, are less commonly associated with neuropathy.
[10:38]
Neuropathy can also be caused by the myeloma protein itself or by complications such as amyloid. Other conditions unrelated to myeloma, including diabetes, autoimmune disease and carpal tunnel syndrome, can also cause or worsen peripheral neuropathy.
[11:16]
Sensory peripheral neuropathy can cause numbness, tingling, prickling and neuropathic pain. Pain is thankfully less common than numbness and tingling, although bortezomib-associated peripheral neuropathy can be painful.
[11:42]
It is important for patients to report any change in sensation. People may say, for example, that their feet feel cold even though they are warm to touch, or that it feels as though they are walking on cauliflowers. These descriptions can alert the treating team to early sensory symptoms and help them decide whether a treatment dose needs to be adjusted.
[12:24]
Neuropathy can also be motor, causing muscle weakness, muscle wasting or cramps. If a person’s gait is affected, there may be an increased risk of falls. Autonomic neuropathy can affect bodily functions and may cause blood pressure issues, bowel and bladder problems or sexual dysfunction.
[13:02]
There is no known treatment that directly protects or repairs the nerves in bortezomib-induced peripheral neuropathy. However, reversible causes such as vitamin B12 deficiency or diabetes should be managed carefully. The dose of bortezomib may be adjusted to reduce symptoms. Patients should also be educated about preventing slips, trips and falls, and exercise can help maintain balance and strength.
[13:44]
Some patients may benefit from acupuncture. Scrambler therapy uses a distracting electrical therapy, similar to a TENS machine, to help people cope with pain.
[14:01]
Medicines that may help manage neuropathic pain include antidepressants such as amitriptyline, nortriptyline and duloxetine. Pregabalin is also commonly used for neuropathy and may be helpful for bortezomib-induced peripheral neuropathy.
[14:29]
Other treatments have their own important adverse effects. Carfilzomib can cause cardiopulmonary problems, particularly cardiomyopathy, so a patient’s heart function should be assessed before treatment. Lenalidomide can cause clotting and diarrhoea. Monoclonal antibodies such as daratumumab and elotuzumab can cause infusion reactions, although premedication is used to reduce or prevent these reactions.
[15:30]
Selinexor has particular side effects including hyponatraemia, gastrointestinal problems and thrombocytopenia, which can significantly affect quality of life.
[15:53]
Corticosteroids, most commonly dexamethasone, can increase blood sugar levels. This is particularly important for people with diabetes, but blood sugar should also be monitored in people without a previous diabetes diagnosis. Dexamethasone can also contribute to weight gain, fluid retention and insomnia.
[16:37]
Lenalidomide-associated diarrhoea is very common but is not always discussed enough. It affects approximately 40 to 54 per cent of patients taking lenalidomide. Chronic diarrhoea can be particularly challenging and may not begin until around 18 months after starting treatment.
[17:12]
The likely mechanism is bile acid malabsorption. Bile acids are normally released into the duodenum after eating food containing fat. In bile acid malabsorption, the bile acids are not properly reabsorbed and remain in the bowel, leading to liquid stools and sometimes more than three episodes of diarrhoea a day.
[17:54]
Other contributing causes may include previous radiotherapy or graft-versus-host disease following an allogeneic transplant. A scan can be used to diagnose bile acid malabsorption, but it is now rarely used or available. Diagnosis is often made by treating the condition and assessing the patient’s response.
[18:30]
When a patient who has been taking lenalidomide for a long time develops diarrhoea, it is important to consider other possible causes. Depending on the circumstances, investigations such as a colonoscopy may be needed to exclude another malignancy or infection.
[18:55]
Bile acid malabsorption may be treated with loperamide to reduce bowel activity, by restricting dietary fats or with a medicine called colestyramine. Colestyramine binds to bile acids in the gastrointestinal tract so that they form a complex and are excreted in the faeces.
[19:36]
Questran, or colestyramine, can interact with other medicines. Other medications are usually taken one hour before or four hours after Questran. Patients should check with their doctor about whether the timing of their medicines needs to change.
[19:59]
Another way to manage the condition is to reduce the lenalidomide dose. This is often considered when the diarrhoea becomes too difficult to manage.
[20:23]
Infection is an important issue in myeloma and can significantly affect quality of life. It is especially common during first-line therapy when the myeloma is highly active, after many lines of treatment, when blood counts are low, when higher or cumulative doses of steroids are used, or when a patient is frail or has kidney impairment.
[20:56]
Patients should know the signs and symptoms of infection and act on them promptly. Preventive antibacterials are sometimes used, particularly Resprim to prevent Pneumocystis pneumonia. Antibiotics are not routinely used preventively in most situations because of the risk of antibiotic resistance.
[21:28]
Growth factors such as G-CSF may be used to increase white blood cell counts. Patients are advised to receive appropriate non-live vaccinations, including influenza, Pneumovax, COVID-19, Shingrix and, where appropriate, respiratory syncytial virus vaccination.
[21:50]
Vaccination of household members can also help because respiratory infections are often contracted from people in the home. Food safety is important to reduce the risk of food poisoning and diarrhoea. Extra caution should also be taken when travelling, and masks and gloves should be used when gardening.
[22:22]
Steroid side effects can affect mood, cataracts, sleep, infection risk, muscle strength, blood sugar, skin thickness, heartburn, blood pressure and fluid retention.
[22:52]
These effects may be managed by reducing, dividing or tapering the steroid dose. Proton pump inhibitors may be used for heartburn, sleeping tablets or non-medicine approaches may help with sleep, and diuretics may be used for fluid retention. Relaxation, dietary changes and exercise can also help reduce steroid side effects.
[23:34]
Experience can help patients learn the pattern of their side effects. Speaking with doctors and other people in a support group can be useful. A symptom journal may also help patients recognise when side effects occur and plan strategies, including exercise, to manage them.
[24:12]
Other supportive treatments include bisphosphonates to help prevent fractures and strengthen bones, blood products, growth factors, antivirals to prevent shingles, Resprim, intravenous or subcutaneous immunoglobulin to help prevent infection, vaccinations, radiotherapy for painful bone lesions, and antiplatelet or anticoagulant medicines to prevent clotting.
[24:51]
I would now like to look at two treatments that can affect quality of life and the measures used to reduce their side effects. For selinexor, Professor King developed guidance on using two anti-nausea medicines. This may include ondansetron together with olanzapine. A combination anti-nausea medicine called Akynzeo is also commonly used with selinexor.
[25:52]
Access to these supportive medicines has become easier as understanding of selinexor has increased. Hydration must be maintained because selinexor can cause low sodium. Patients may also be advised to eat salty snacks and increase their calorie intake, sometimes with support from a dietitian.
[26:32]
Belantamab is another treatment that we hope will become available as standard care. The main concern is its effect on the eyes. Myeloma doctors understand how frequently eye checks are needed, and a hub-and-spoke model involving optometrists and ophthalmologists may help manage these side effects and preserve vision.
[27:21]
Eye drops and dose adjustments are important when using belantamab. Evidence from trials and subsequent work suggests that the starting dose may be reduced while maintaining effectiveness and reducing the severity of side effects.
[27:48]
Finally, promoting a healthy lifestyle is important for improving quality of life. This includes maintaining good nutrition, making sleep a priority, not smoking, identifying and reducing sources of stress, using support services such as counsellors and clinical psychologists, and exercising. Exercise is increasingly recognised as having wide-reaching health benefits in cancer and beyond.
[28:25]
I have now come to the end of my talk. I would like to acknowledge my team, particularly Professor Tracy King, as well as my colleagues in the research and clinical units. I would also like to thank Myeloma Australia for inviting me to speak. Thank you.
