Myeloma: diagnosis and management

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 doing 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.

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

When doing 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.

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

Consider whole‑body MRI as first‑line imaging.

Consider whole‑body low‑dose CT as first‑line imaging if whole‑body MRI is unsuitable or the person declines it.

Consider skeletal survey as first‑line imaging only 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.

For people with newly diagnosed myeloma or smouldering myeloma who have not had whole‑body imaging with 1 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.

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 NICE technology appraisal guidance on 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. [This recommendation is from NICE technology appraisal guidance on bortezomib and thalidomide for the first-line treatment of multiple myeloma.]

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. [This recommendation is from NICE technology appraisal guidance on bortezomib and thalidomide for the first-line treatment of multiple myeloma.]

Consider bortezomib‑based, lenalidomide‑based, or both, 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 it is suitable.

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.

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 line with the NICE guideline on assessing the risk of fragility fractures in osteoporosis) 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.

For guidance on treating metastatic spinal cord compression, see the NICE guideline on metastatic spinal cord compression.

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, when relevant, using the NICE guidelines on neuropathic pain and opioids in palliative care.

Consider the following, in addition to other treatments, for all people with myeloma and spinal bone disease:

• interventional pain management

• bracing.

For 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.

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 aciclovir or equivalent antiviral prophylaxis after treatment with bortezomib or other proteasome inhibitors ends.

In February 2016, this was an off-label use. See NICE's information on prescribing medicines.

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

In February 2016, this was an off-label use. See NICE's information on prescribing medicines.

Consider testing for hepatitis B, hepatitis C and HIV before starting myeloma treatment.

For guidance on the pharmacological management of neuropathic pain see the NICE guideline on neuropathic pain in adults.

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 doing 1 or more of the following:

• switching to subcutaneous injections

• reducing to weekly doses

• 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.

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

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). [This recommendation is from NICE technology appraisal guidance on bortezomib monotherapy for relapsed multiple myeloma.]

People currently receiving bortezomib monotherapy who do not meet the criteria in recommendation 1.10.1 should have the option to continue therapy until they and their clinicians consider it appropriate to stop. [This recommendation is from NICE technology appraisal guidance on bortezomib monotherapy for relapsed multiple myeloma.]

Offer a second autologous stem cell transplant, if it is suitable, to people with relapsed myeloma who have:

• completed re‑induction therapy without disease progressionand

• had a response duration of more than 24 months after their first autologous stem cell transplant.

Consider a second autologous stem cell transplant, if it is suitable, for people with relapsed myeloma who have:

• completed re-induction 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 a second autologous stem cell transplant is more likely to be suitable for people with relapsed myeloma if they have:

• had a good response to the first autologous stem cell transplant

• a lower International Staging System (ISS) stage

• not had many prior treatments

• good overall fitness, based on resilience, frailty and performance status

• no adverse fluorescence in‑situ hybridisation (FISH) results.

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. [This recommendation is from NICE technology appraisal guidance on lenalidomide for the treatment of multiple myeloma in people who have received at least one prior therapy.]

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. [This recommendation is from NICE technology appraisal guidance on lenalidomide for the treatment of multiple myeloma in people who have received at least one prior therapy.]

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. [This recommendation is from NICE technology appraisal guidance on pomalidomide for relapsed and refractory multiple myeloma previously treated with lenalidomide and bortezomib.]

People whose treatment with pomalidomide was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop. [This recommendation is from NICE technology appraisal guidance on pomalidomide for relapsed and refractory multiple myeloma previously treated with lenalidomide and bortezomib.]