Thursday, April 24, 2014

This is an extract from an article written for a medical journal by MSAG member Dr Hang Quach and reproduced here with her permission. The original article was intended for medical practitioners not all of whom would have been familiar with multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy characterised by the presence of serum and /or urine paraprotein as a result of clonal expansion of plasma cells. It is a disease of the elderly, with a median age at diagnosis of 65-70 years. Approximately 1200 cases are diagnosed in Australia each year, and the reported incidence is increasing. Although MM has become more treatable over the last decade, it remains incurable and is a condition riddled with morbidity, both from disease-related systemic complications as well as treatment-related side effects. Given that patients are usually managed in an outpatient setting, the role of the local medical officer (LMO) in joint care with the treating specialist, is vital in ensuring optimal supportive care, and delivery of preventative/treatment measures for potential disease/treatment-related complications. As such, familiarity with the current standard treatment of this disease and the potential complications would optimise patient management in the community.

What is the current standard treatment for patients with multiple myeloma?

The decision to commence treatment is based on the presence of myeloma related organ tissue injury (ROTI). Patients without ROTI fall into the category of asymptomatic myeloma. These patients are simply observed, as there is no evidence of survival benefit with early treatment. Patients with symptomatic MM are those with MM related organ damage. Treatment choices for these patients are dependent on both age and the presence of comorbidities. Patients aged ≤65 years are usually given 3 to 4 cycles of induction therapy followed by autologous stem cell transplant (AuSCT) upfront. Patients aged ≥75 are deemed not eligible for AuSCT, and are given oral chemotherapy in combination with a novel therapeutic agent [thalidomide, lenalidomide (Revlimid), bortezomib (Velcade)]. Treatment for patients aged between 65-75 are individualised based on clinical assessment. Currently, the standard treatment in Australia for patients ineligible for AuSCT, is combination oral mephalan, prednisolone, and thalidomide (MPT). Lenalidomide and bortezomib have also shown impressive efficacy in combination with melphalan and prednisolone, however, these agents are not available for MM upfront treatment on the PBS.

What are the common complications from multiple myeloma and important supportive issues?

Bony destruction: This is mediated by cytokines that are induced by plasma cell growth, which promotes osteoclastic activity and down regulate osteoblastic activity. Bone complications such as lytic lesions, crush fractures, and osteoporosis, are seen in over 70% of patients at presentation. Patients are managed with bisphosphonates, usually either monthly IV infusions of zolendronate or pamidronate, or oral sodium clondronate (bonefos). Calcium and vitamin D supplementation should be given to patients on bisphosphonate in consultation with the treating specialist. Due to the risk of ONJ (osteonecrosis of the jaw: a condition characterised by non-healing wound post dental surgery associated with long term use of IV bisphosphonates), all patients should have full dental review prior to bisphosphonate initiation. Bisphophosphonates should be discontinued for 2-3 months before and after any dental extraction/surgery.

Renal impairment: Renal impairment confers a poor prognosis in MM, and severe impairment is present in approximately 20% of MM patients at presentation. It is mediated via a combination of light chain-induced renal toxicity, cast nephropathy, other deposition disease, and exacerbated by dehydration or hypercalcaemia. Restoration of renal function has been shown to improve prognosis. Patients should avoid nephrotoxic drugs and encouraged to increase fluid intake up to 2L per day.

Anaemia: This occurs in over 80% of MM patients and is due to a combination of bone marrow replacement, renal impairment, and anaemia of chronic disease. Patients are encouraged to maintain a healthy balanced diet. Blood transfusions or subcutaneous injections of recombinant erythropoietin may be appropriate in patients with symptomatic anaemia and renal impairment respectively, in consultation with the treating specialist.

Infections: MM patients are immunosuppressed due to a combination of hypogammaglobulinaemia, dysfunctional lymphocytes, and immunosuppressive treatments. Patients are encouraged to present early with infections for prompt antibiotic treatments. Those with recurrent chest infections and hypogammaglobulinaemia may benefit from monthly IVIg infusions in consultation with the treating specialist. Patients on high dose prednisolone (equivalent to 20mg prednisolone daily for weeks) should have PCP (pneumocystis carinii) prophylaxis such as Bactrim DS. Prophylaxis against Varicella Zoster reactivation (eg. Valacyclovir) should be given to patients receiving bortezomib (Velcade), especially when it is used in combination with corticosteroids.

Hypercalcaemia: This occurs from bone resorption in progressive MM, and should be considered in patients with polyuria, constipation, abdominal pain and in severe cases, confusion and renal failure. Patients should be referred promptly for admission for IV hydration and specific calcium lowering measures to avoid renal failure.‑‑‑

Venothromboembolism (VTE): The incidence of VTE is ~1% annually in the general population and is increased up to 10 fold in malignancy. In MM, this is exacerbated by the use of thalidomide and lenalidomide. Thalidomide alone does not increase the risk of VTE (incidence ~3-4%), but the risk increases to 14-26% in combination with dexamethasone, and up to approximately 30% when used in combination with chemotherapy.

Lenalidomide, like thalidomide, does not appear to significantly increase the risk of VTE as a single agent. In combination with dexamethasone or chemotherapy however, VTE risk increases in the order of ~ 14-16%. MM patients treated with thalidomide or lenalidomide should have VTE prophylaxis with aspirin (75-300mg daily), low molecular weight heparin (equivalent of enoxaparin 40mg daily) or full dose warfarin (target INR 2-3). The choice is dependent on VTE risk assessment by the treating specialist.

Table 1: Common side effects of novel therapeutic agents.   

 

Side effects

 

Peripheral neuropathy

 

All Grades

 

Somnolence/sedation

 

Constipation

 

Diarrhoea

 

Fatigue

 

Thomboembolism

 

Bradycardia

 

Varicella zoster

 

Haematological toxicities:

 

Grade 3-4

 

Teratogenicity

 

Thalidomide

 

28%

 

-Mostly sensory

 

-Cumulative toxicity limiting dose and duration of treatment.

 

-Can be irreversible.

 

>50%

 

>50%

 

Rare

 

>50%

 

5-30%*

 

6%

 

Not reported.

 

Neutropenia: 11%

 

Yes

 

Lenalidomide

 

<5%

 

Rare

 

<5%

 

<5%

 

<10%

 

8-15%

 

Not reported

 

Not reported

 

Thrombocytopenia: 10%.

 

Neutropenia:

 

24%-27%

 

Unknown (but same precaution as thalidomide.

 

Bortezomib

 

37%

 

-Predominantly sensory.

 

-Responds to dose reduction.

 

-Reversible in the majority of patients.

 

Not reported

 

42%

 

57%

 

42%

 

<1%

 

<1%

 

Single agent:11-13%

 

With dexamethasone combination:19%

 

Thrombocytopenia: 30%

 

Neutropenia:14%

Not reported in animal models.

What patient supports are available in the community?

The Myeloma Foundation of Australia is a non-profit organisation that runs seminars, support groups and education for patients, carers and health professionals.

The support nurse can be contacted by patients on 1800MYELOMA (1800 693 566, Mon-Fri working hours). Website www.myeloma.org.au


The Myeloma Foundation of Australia Inc, ABN 30 476 390 368 "MY Foundation" is passionate about assisting and improving the quality of life of Australians living with myeloma. MY Foundation understands the myeloma experience and empathises with patients and family members. At MY Foundation the needs of people with myeloma will always come first. MY Foundation will always deliver an organised and professional operation ... and operate in an inclusive and transparent manner.


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