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National and International Guidance (as of 2023) is out of date with current practice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.