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Nice Guidelines on Diagnosis and Management of Myeloma 2016


Nice Guidelines on Diagnosis and Management of Myeloma 2016

Myeloma is a type of cancer that develops from cells in the bone marrow called plasma cells. Bone marrow is the spongy tissue found inside the inner part of some of our large bones. The bone marrow produces different types of blood cells.

Myeloma can develop wherever there are plasma cells. So it can be anywhere there is bone marrow, including the pelvis, spine and ribcage. As it can occur in several places in the body, it is often called multiple myeloma.

National Collaborating Centre for Cancer  and the National Institute for Health and Care Excellence (NICE) have published a clinical practice guideline on  Myeloma: diagnosis and management-2016 . Following are its major recommendations:

Communication and Support

Provide information and support to people with myeloma or primary plasma cell leukaemia and their family members or carers (as appropriate), particularly at diagnosis, at the beginning and end of each treatment, at disease progression and at transition to end of life care.

Consider providing the following information in an individualised manner to people with myeloma and their family members or carers (as appropriate):

  • The disease process, relapse and remission cycle, and the person’s overall prognosis
  • The treatment plan, including (if appropriate) the process and the potential benefits, risks and complications of stem cell transplantation
  • Symptoms of myeloma and treatment-related side effects (including steroid-related side effects, infection and neuropathy)
  • Lifestyle measures to optimise bone health and renal function
  • How to identify and report new symptoms (especially pain and spinal cord compression)
  • The role of supportive and palliative care
  • How to access peer support and patient support groups

Offer prompt psychological assessment and support to people with myeloma at diagnosis and (as appropriate) at the beginning and end of each treatment, at disease progression and at transition to end of life care.

Refer people who are assessed as needing further psychological support to psychological services.

Advise family members or carers (as appropriate) about the range of available local and national support services at diagnosis, at the beginning and end of each treatment, at disease progression and at transition to end of life care.

Laboratory Investigations

Laboratory Investigations for People with Suspected Myeloma

Use serum protein electrophoresis and serum-free light-chain assay to confirm the presence of a paraprotein indicating possible myeloma or monoclonal gammopathy of undetermined significance (MGUS).

If serum protein electrophoresis is abnormal, use serum immunofixation to confirm the presence of a paraprotein indicating possible myeloma or MGUS.

Do not use serum protein electrophoresis, serum immunofixation, serum-free light-chain assay or urine electrophoresis (urine Bence–Jones protein assessment) alone to exclude a diagnosis of myeloma.

When performing a bone marrow aspirate and trephine biopsy to confirm a diagnosis of myeloma, use morphology to determine plasma cell percentage and flow cytometry to determine plasma cell phenotype.

For guidance on the setup of laboratory diagnostic services see the NICE cancer service guidance on improving outcomes in haematological cancers External Web Site Policy.

Laboratory Investigations to Provide Prognostic Information

Use the same sample for all diagnostic and prognostic tests on bone marrow, so people only have to have one bone marrow aspirate and trephine biopsy.

When performing a bone marrow aspirate and trephine biopsy to provide prognostic information:

  • Perform fluorescence in-situ hybridisation (FISH) on CD138-selected bone marrow plasma cells to identify the adverse risk abnormalities t(4;14), t(14;16), 1q gain, del(1p) and del(17p)(TP53 deletion). Use these abnormalities alongside International Staging System (ISS) scores to identify people with high-risk myeloma.
  • Consider performing FISH on CD138-selected bone marrow plasma cells to identify the adverse risk abnormality t(14;20), and the standard risk abnormalities t(11;14) and hyperdiploidy.
  • Consider performing immunophenotyping of bone marrow to identify plasma cell phenotype, and to inform subsequent monitoring.
  • Consider performing immunohistochemistry (including Ki-67 staining and p53 expression) on the trephine biopsy to identify plasma cell phenotype and give an indication of cell proliferation, to provide further prognostic information.

Perform serum-free light-chain assay and use serum-free light-chain ratio to assess prognosis.

Imaging Investigations

Imaging for People with Suspected Myeloma

Offer imaging to all people with a plasma cell disorder suspected to be myeloma.

Consider whole-body magnetic resonance imaging (MRI) as first-line imaging.

Consider whole-body low-dose computed tomography (CT) as first-line imaging if whole-body MRI is unsuitable or the person declines it.

Only consider skeletal survey as first-line imaging if whole-body MRI and whole-body low-dose CT are unsuitable or the person declines them.

Do not use isotope bone scans to identify myeloma-related bone disease in people with a plasma cell disorder suspected to be myeloma.

Imaging for People with Newly Diagnosed Myeloma

For people with newly diagnosed myeloma or smouldering myeloma who have not had whole-body imaging with one of the following, consider whole-body imaging to assess for myeloma-related bone disease and extra-medullary plasmacytomas with one of:

  • MRI
  • CT
  • Fluorodeoxyglucose positron emission tomography CT (FDG PET-CT).

Consider baseline whole-body imaging with MRI or FDG PET-CT for people who have non-secretory myeloma or suspected or confirmed soft tissue plasmacytomas and have not already had either of these tests.

Service Organisation

Each hospital treating people with myeloma who are not receiving intensive inpatient chemotherapy or a transplant should provide local access to:

  • An MDT specialising in myeloma
  • Supportive and palliative care, supported by:
    • Psychological support services
    • A 24-hour acute oncology and/or haematology helpline
    • Physiotherapy
    • Occupational therapy
    • Dietetics
    • Medical social services
    • Critical care
  • Clinical trials via the MDT specialising in myeloma
  • Dental services

Each hospital treating people with myeloma should provide regional access through its network to:

  • Facilities for intensive inpatient chemotherapy or transplantation
  • Renal support
  • Spinal disease management
  • Specialised pain management
  • Therapeutic apheresis
  • Radiotherapy
  • Restorative dentistry and oral surgery
  • Clinical trials, in particular early phase trials

Managing Newly Diagnosed Myeloma

First-line Treatment

Bortezomib is recommended as an option within its marketing authorisation, that is, in combination with dexamethasone, or with dexamethasone and thalidomide, for the induction treatment of adults with previously untreated multiple myeloma, who are eligible for high-dose chemotherapy with haematopoietic stem cell transplantation. [This recommendation is from the NGC summary of the NICE guideline Bortezomib for induction therapy in multiple myeloma before high-dose chemotherapy and autologous stem cell transplantation.

Thalidomide in combination with an alkylating agent and a corticosteroid is recommended as an option for the first-line treatment of multiple myeloma in people for whom high-dose chemotherapy with stem cell transplantation is considered inappropriate.

Bortezomib in combination with an alkylating agent and a corticosteroid is recommended as an option for the first-line treatment of multiple myeloma if:

  • High-dose chemotherapy with stem cell transplantation is considered inappropriate and
  • The person is unable to tolerate or has contraindications to thalidomide

First Autologous Stem Cell Transplantation

Consider using frailty and performance status measures that include comorbidities to assess the suitability of people with myeloma for first autologous stem cell transplant.

Do not use age or the level of renal impairment alone to assess the suitability of people with myeloma for first autologous stem cell transplant.

Allogeneic Stem Cell Transplantation

Take into account that only a small number of people with myeloma are suitable for allogeneic stem cell transplantation.

When assessing whether people with myeloma are suitable for an allogeneic stem cell transplant, take into account:

  • Whether the person has chemosensitive disease
  • How many previous lines of treatment they have had
  • Whether a fully human leukocyte antigen (HLA) matched donor is available
  • How graft-versus-host disease (GvHD) and other complications may get worse with age
  • The risk of higher transplant-related mortality and morbidity, versus the potential for long-term disease-free survival
  • Improving outcomes with other newer treatments
  • The person’s understanding of the procedure and its risks and benefits

Consider allogeneic stem cell transplantation as part of a clinical trial if one is available.

Primary Plasma Cell Leukaemia

Consider bortezomib-based and/or lenalidomide-based combination induction chemotherapy for people with primary plasma cell leukaemia.

Consider high-dose melphalan-based autologous stem cell transplantation for people with primary plasma cell leukaemia if they are suitable.

Managing Acute Renal Disease Caused by Myeloma

Consider immediately starting a bortezomib- and dexamethasone-based combination regimen for people with untreated, newly diagnosed, myeloma-induced acute renal disease.

If a bortezomib-based combination regimen is unsuitable for people with untreated, newly diagnosed, myeloma-induced acute renal disease, consider immediately starting a thalidomide- and dexamethasone-based combination regimen1.

Do not perform plasma exchange for myeloma-induced acute renal disease.

Preventing and Managing Bone Disease

Preventing Bone Disease

To prevent bone disease, offer people with myeloma:

  • Zoledronic acid or
  • Disodium pamidronate, if zoledronic acid is contraindicated or not tolerated or
  • Sodium clodronate, if zoledronic acid and disodium pamidronate are contraindicated, not tolerated or not suitable

Consider immediately referring people with myeloma for dental assessment and treatment before starting zoledronic acid or disodium pamidronate.

For people who need urgent myeloma treatment, consider referring for dental assessment and treatment as soon as possible after they start treatment.

Managing Non-spinal Bone Disease

Offer people with myeloma and non-spinal bone disease who have not already started bisphosphonates:

  • Zoledronic acid or
  • Disodium pamidronate, if zoledronic acid is contraindicated or not tolerated or
  • Sodium clodronate, if zoledronic acid and disodium pamidronate are contraindicated, not tolerated or not suitable

Assess the risk of fracture in people with myeloma and non-spinal bone disease.

Consider surgical stabilisation followed by radiotherapy for non-spinal bones that have fractured or are at high risk of fractures.

Consider radiotherapy for non-spinal bones that have fractured or are at high risk of fracture if surgical intervention is unsuitable or not immediately needed.

Consider radiotherapy for people with myeloma and non-spinal bone disease who need additional pain relief if:

  • Chemotherapy and initial pain management has not led to prompt improvement in pain control
  • Chemotherapy is unsuitable and current pain medication is not working

Consider re-treatment with radiotherapy if pain recurs or if there is regrowth of a previously treated lesion.

Consider seeking advice from or referral to specialists in palliative care or pain medicine for people with complex non-spinal bone disease.

Managing Spinal Bone Disease

Offer all people with myeloma and spinal bone disease:

  • Bisphosphonates as follows, if not already started:
    • Zoledronic acid or
    • Disodium pamidronate, if zoledronic acid is contraindicated or not tolerated or
    • Sodium clodronate, if zoledronic acid and disodium pamidronate are contraindicated, not tolerated or unsuitable
  • Systemic pain control

Consider the following as adjuncts to other treatments for all people with myeloma and spinal bone disease:

  • Interventional pain management
  • Bracing

In people with radiological evidence of myeloma-related spinal instability, consider immediate intervention with:

  • Spinal surgery, with or without radiotherapy
  • Cement augmentation, with or without radiotherapy
  • Radiotherapy alone, if spinal intervention is unsuitable or not currently needed

In people with radiological evidence of myeloma-related spinal bone disease without instability, consider:

  • Cement augmentation, with or without radiotherapy
  • Radiotherapy alone

Preventing and Managing Complications

Preventing Infection

Offer people with myeloma the seasonal influenza vaccination.

Consider extending the pneumococcal vaccination to people with myeloma who are under 65.

Consider intravenous immunoglobulin replacement therapy for people who have hypogammaglobulinaemia and recurrent infections.

Consider continuing aciclovir2 or equivalent antiviral prophylaxis after treatment with bortezomib or other proteasome inhibitors ends.

Consider aciclovir2 or equivalent antiviral prophylaxis for people who are taking both immunomodulatory drugs and high-dose steroids.

Consider testing for hepatitis B, hepatitis C and human immunodeficiency virus (HIV) before starting myeloma treatment.

Managing Peripheral Neuropathy

Explain the symptoms of neuropathy to people with myeloma, and encourage them to tell their clinical team about any new, different or worsening neuropathic symptoms immediately.

If people who are receiving bortezomib develop neuropathic symptoms, consider immediately:

  • Switching to subcutaneous injections and/or
  • Reducing to weekly doses and/or
  • Reducing the dose

Consider reducing the dose if people are taking a drug other than bortezomib and develop neuropathic symptoms.

Temporarily stop neuropathy-inducing myeloma treatments if people develop either of the following:

  • Grade 2 neuropathy with pain
  • Grade 3 or 4 neuropathy

If neuropathy does not improve despite stopping myeloma treatment and further treatment is needed, consider switching to myeloma treatments less likely to induce neuropathy.

Preventing Thrombosis

For people with myeloma who are starting immunomodulatory drugs, offer thromboprophylaxis with either:

  • Low molecular weight heparin (LMWH) at a prophylactic dose, or
  • Vitamin K antagonists at a therapeutic dose, to maintain an international normalised ratio (INR) of 2–3

If LMWH or vitamin K antagonists are unsuitable, consider low-dose aspirin3.

When starting thromboprophylaxis, assess the risk factors, contraindications and practicalities of each prophylactic strategy.

Do not offer fixed low-dose vitamin K antagonists for thromboprophylaxis to people with myeloma who are starting immunomodulatory drugs.

Consider switching thromboprophylaxis to low-dose aspirin for people who:

  • Are taking immunomodulatory drugs and
  • Have achieved maximum response and
  • Have no high risk factors

Managing Fatigue

If other treatable causes of anaemia have been excluded, consider erythropoietin analogues (adjusted to maintain a steady state of haemoglobin at 110–120 g/litre) to improve fatigue in people with myeloma who have symptomatic anaemia.

Monitoring

Monitor people with smouldering myeloma every 3 months for the first 5 years, and then decide the frequency of further monitoring based on the long-term stability of the disease.

Monitor people who have completed myeloma treatment and recovered at least every 3 months. Take into account any risk factors for progression, such as:

  • High-risk FISH
  • Impaired renal function
  • Disease presentation

Monitoring for myeloma and smouldering myeloma should include:

  • Assessment of symptoms related to myeloma and myeloma treatment and
  • The following laboratory tests:
    • Full blood count
    • Renal function
    • Bone profile
    • Serum immunoglobulins and serum protein electrophoresis
    • Serum-free light-chain assay, if appropriate

Do not offer people with myeloma or smouldering myeloma routine skeletal surveys for disease monitoring.

Consider symptom-directed imaging for people with myeloma or smouldering myeloma if any new bone symptoms develop.

For people with myeloma and serological relapse or disease progression, consider one of the following (taking into consideration previous imaging tests):

  • Whole-body MRI
  • Spinal MRI
  • FDG PET-CT

For people with smouldering myeloma and disease progression, consider one of the following (taking into consideration previous imaging tests):

  • Whole-body MRI
  • Whole-body low-dose CT
  • Whole-body CT
  • Spinal MRI
  • FDG PET-CT

Managing Relapsed Myeloma

First Relapse

Bortezomib monotherapy is recommended as an option for the treatment of progressive multiple myeloma in people who are at first relapse having received 1 prior therapy and who have undergone, or are unsuitable for, bone marrow transplantation, under the following circumstances:

  • The response to bortezomib is measured using serum M protein after a maximum of 4 cycles of treatment, and treatment is continued only in people who have a complete or partial response (that is, reduction in serum M protein of 50% or more or, where serum M protein is not measurable, an appropriate alternative biochemical measure of response), and
  • The manufacturer rebates the full cost of bortezomib for people who, after a maximum of 4 cycles of treatment, have less than a partial response (as defined above).

People currently receiving bortezomib monotherapy who do not meet the criteria in recommendation above should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

Second Autologous Stem Cell Transplantation

Offer a second autologous stem cell transplant to people with relapsed myeloma who are suitable and who have:

  • Completed re-induction therapy without disease progression and
  • Had a response duration of more than 24 months after their first autologous stem cell transplant

Consider a second autologous stem cell transplant for people with relapsed myeloma who are suitable and who have:

  • Completed reinduction therapy without disease progression and
  • Had a response duration of between 12 and 24 months after their first autologous stem cell transplant

Be aware that people with relapsed myeloma are more likely to be suitable for a second autologous stem cell transplant if they have:

  • Had a good response to the first autologous stem cell transplant
  • A lower ISS stage
  • Not had many prior treatments
  • Good overall fitness, based on resilience, frailty and performance status
  • No adverse FISH results

Subsequent Therapy

Lenalidomide in combination with dexamethasone is recommended, within its licensed indication, as an option for the treatment of multiple myeloma only in people who have received two or more prior therapies, with the following condition:

  • The drug cost of lenalidomide (excluding any related costs) for people who remain on treatment for more than 26 cycles (each of 28 days; normally a period of 2 years) will be met by the manufacturer.

People currently receiving lenalidomide for the treatment of multiple myeloma, but who have not received 2 or more prior therapies, should have the option to continue therapy until they and their clinicians consider it appropriate to stop

Pomalidomide, in combination with dexamethasone, is not recommended within its marketing authorisation for treating relapsed and refractory multiple myeloma in adults who have had at least 2 previous treatments, including lenalidomide and bortezomib, and whose disease has progressed on the last therapy.

For detailed guidelines refer to https://www.nice.org.uk

 


Source: National Collaborating Centre for Cancer. Myeloma: diagnosis and management. London (UK): National Institute for Health and Care Excellence (NICE); 2016 Feb 10. 25 p. (NICE guideline; no. 35).

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