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Supportive Care & late effects in myeloma (bsh 2011, bsh 2017)
intro
National guidance is long in tooth (2011!) —> Make sure to know your hospital’s local practice
Starting Point —> MDT Approach – Palliative Care, Pain Management, Clinical Oncology, Orthopaedics etc
Anaemia
Present in 75% patients at diagnosis
Blood transfusion and/or Erythropoiesis-Stimulating Agents (ESAs)
ESAs recommended for anaemia in myeloma with associated renal impairment
E.g. Darbepoetin 6.25ug/kg every 3 weeks
True or functional iron deficiency occurring during ESA therapy should be treated with IV iron infusions
Bleeding
Rare at presentation, usually occurring later as a result of:
Thromobocytopenia (immune or marrow infiltration), renal failure, infection, therapy toxicity, acquired von Willebrands, fibrin defects, hyperfibrinolysis, heparin-like anticoagulants and factor X deficiency (in AL amyloidosis)
No consensus on treatment of acquired VWD in myeloma – desmopression, IVIg and factor concentrates have all been used.
Thrombosis
National and International Guidance (as of 2023) is out of date with current practice
Highest VTE risk is in newly diagnosed patients & those treated with IMIDs
Despite introduction of LMWH thromboprophylaxis, VTE rate remains 10% in first 6 months of treatment with Thalidomide or Lenalidomide.
In patients receiving IMiD’s
Practice has largely moved to prophylactic doses of DOACs on basis of convenience / QoL
Now several single centre studies demonstrating safety and non-inferiority of apixaban vs LMWH
Larger, or randomised, data still awaited (as of 2023)
Infection
10% of patients die of infection within 60 days of diagnosis
Myeloma patients have inadequate responses to a variety of vaccines, esp polysaccharide
‘Flu, Step pneumonia and Haemophilus vaccines are recommended
Consider prophylactic IVIg
Aciclovir prophylaxis for bortezomib-based regimens or post-autograft
Pain
Multifactorial – destructive bone disease, plasmacytoma, co-morbidities, drug side effects (e.g. GCSF), mucositis, neuropathies
Cause may not be clear – e.g. neuropathy ?Chemo ?Diabetes ?Carpal tunnel
Titrating opiates
Normal release can be increased by 30-50% daily
Sustained release every 2-3 days
Patches every 3 days
Patches work well in myeloma – give anti-emetic for first 7 days of buprenorphine
Opioid-induced hyperalgesia
Increased pain with increasing dose, usually at original site of pain + adjacent dermatomes
Radiotherapy
Myeloma is usually radio-responsive
8 Gy single fraction often an appropriate dose for pain control
Bisphosphonate Bone Protection
Zometa
>60ml/min: 4.0mg
50-60ml/min: 3.5mg
40-49ml/min: 3.3mg
30-39ml/min: 3.0mg
<30ml/min: Do not give
Pamidronate
Consider if Zometa contraindicated
Peripheral Neuropathy
Causes
Disease-associated – spinal cord or nerve root compression, POEMS
M-protein-associated – seen in MGUS more than myeloma
Co-morbidities – diabetes, carpal tunnel, CIDP, renal failure, B12 deficiency
Chemotherapy
Thalidomide – cumulative effect, mild-moderate, improves with stopping
Bortezomib – length-dependent distal sensory neuropathy with suppression of reflexes + motor & autonomic neuropathies. May take 2 years to resolve
Management
Correct the cause
Dose-adjust chemo as per SPC
L/S BP prior to bortez dose detects autonomic neuropathy before severe
Capsaicin cream acts on peripheral nerve TRPV1 (menthol on TRPM8)
Lidocaine patch
Nausea and Vomiting
Many causes – hypercalcaemia, analgesia, chemotherapy
Pro-kinetcs good for acute emesis
Consider ondansetron (5HT3 antagonist) for severe chemo nausea
Bisphosphonate osteonecrosis of the jaw
Presence of exposed necrotic bone in the mandible that does not heal after 2 months
RF – LT bisphos use, dental surgery, prior malignancies, smoking
Management is supportive, occasionally debridement required
End of Life
See guideline for more info. All the standard procedures.
Others to be aware of
Anorexia
Constipation/diarrhoea
Mucositis
Sedation
Fatigue – treatable causes include anaemia, low testosterone, thyroid def, drugs
Late Complications of Myeloma
Myeloma survival is increasing and so need to address side effects of treatment, co-morbidities and the impact of the physical disease and its treatments on psychological and social wellbeing.
Late Effects = A health problem that occurs months or years after a disease is diagnosed or after treatment has ended. Late effects may be caused by cancer or cancer treatment. They include physical, mental and social problems.
Survivorship = a focus on the health and life of a person with cancer post treatment until the end of life. It covers physical, psychosocial and economic issues of cancer, beyond the diagnosis and treatment phases.
Myeloma Survival – 5-year relative survival rate rose from 20% in 1995 to 40% in 2011.
Long-term Physical consequences
Infection and Immunity
Quantitative and qualitative defects in B cells, T cell subsets, NK and dendritic cells
Compounded by treatment-induced immunosuppression, neutropenia, immobility
Most myeloma patients die from infection, included 10% within 60 days of diagnosis
Management
Pomalidomide ass. w/ 30% risk of infection —> prophylactic Abx for 1st 3 months
Levofloxacin or moxifloxacin should be used (cipro contraindicated)
Aciclovir if bortezomib, lenalidomide or previous shingles
Fluconazole with high dose steroids (prevention of oesophageal candidiasis)
IVIg replacement on a patient-by-patient basis
Vaccination
Aim to vaccinate between courses of treatment, more effective then
Flu + Pneumococcal (PCV13 and PPV23) + Hib are recommended
Other available in activated vaccines include: DTP, Hep A, Hep B, Meningococcal, Typhoid, Pertussis
Renal and Urogenital
50% of patients have renal impairment at presentation
Causes: Cast nephropathy, infection, dehydration, hypercalcaemia, hyperuricaemia, NSAIDs, AL amyloidosis
Management
Optimise diabetes and blood pressure control to prevent further renal injury
Appropriate dose reductions
ESAs
Bone, Endocrine and Metabolic
Bone loss causes – lytic lesions, chemotherapy, steroids, vit D deficiency, inactivity, hypogonadism, renal failure and 2o hyperparathyroidism, radiotherapy
Bone Loss Management
Zolendronic acid – reduces fractures, preserves density and prolongs PFS / OS
Calcium and Vit D supplementation, hormone replacement
Endocrine
9% hypothyroidism, 65% hypogonadism in male patient, sarcopenic obesity
Management – active screening
BMI, waist circumference, strength, BP, HbA1c, lipid profiles
Weight bearing exercises as part of a structured rehab course
Neurological and Eye Complications
Spinal Cord or nerve root compression is the most common neurological presenting Sx
Chemotherapy-Induced Peripheral Neuropathy (CIPN) most common LT neuro problem
Polyneuropathies may be 2o to myeloma, POEMS, AL amyloidosis
2o to co-morbidities – diabetes, carpal tunnel, CKD, Vitamin deficiencies
Eyes – cataracts post steroids and transplant conditioning, diabetic retinopathy
Management
Pain specialist, gabapentin
Cardiovascular & respiratory
50% of patients have ECG / Echo / BNP / Lung function test abnormalities
Associated with a poorer QoL
Resp function – recurrent infection, PE, chemotherapy, radiotherapy, hypoventilation due to bone pain, smoking
Cardiac function – sodium and fluid retaining effects of steroids and IMiDs, cardiac amyloid, anaemia, raised BMI
Management
Lifestyle management
ESAs / transfusion to correct anaemia
Oral and Dental Hygiene
Bisphosphonate-related osteonecrosis of the jaw (BRONJ)
Oral dryness 2o to chemoradiotherapy, supportive meds
Leads to dental infection, altered taste, speaking and swallowing difficulty
Management
Annual dental review, artificial saliva
Gastrointestinal and Nutritional problems
Bowel disturbance is a persistent side effect of many chemotherapies
Diarrhoea with lenalidomide due to bile acid malabsorption and responds to bile acid sequestrants (cholestyramine)
Common nutritional deficiencies
Vit B12, Vit D, Folate
Management
Monitor weight, involve dietitians, routinely assess drug and alcohol history
Second Primary Malignancies
8-11 fold increased risk of MDS & AML over general population
Management
Encourage participation in NHS cancer screening
Skin care
Frailty, Psychosocial and Rehabilitation Considerations
Definitions
Frailty – A phenotype (3 or more of weakness, poor endurance, weight loss, low physical activity, slow gait speed) (2001) or the cumulative effect of individual deficits (2007)
Disability – difficulty or dependency in carrying out activities essential to independent living including task needed for self-care and desired activities important to one’s quality of life
Comorbidity – concurrent presence of 2 or more medically diagnosed disease in the same person, with the diagnosis of each contributing disease based on established criteria
Three aims of assessment
1. Predict toxicity (—> dose modification)
2. Provide prognostic information
3. Detect disability (—> support it)
Geriatric Assessment (GA) Tools
Many available, no one tool shown to be best in oncology
GA tools detect age-related problems missed in history&exam in 50% of patients
Performance status underestimates the degree of disability
A frailty score includes age, comorbidities and GA
Psychological Wellbeing
At time of diagnosis, 8% anxiety and 24% depression reported
50% of these patients had a desire for psychosocial interventions including relaxation techniques, counseling and peer support groups
A suggested “Late Effects MDT”
Core team – lead clinician, nurse specialist, physio, OT and psychologist
Associates – GP, Geriatrician, Psychiatrist, Endocrinologist, Cardiologist, Immunologist, Renal, Gastro, REsp, Neuro, Ophthal, Dermaholiday, Pscyhosexual counselor, Palliative care
Social / voluntary – Social worker, patient support group, cancer information services, Citizens Advice, Cancer /Elderly charities, complementary therapies.