Multiple Myeloma

Unified UK clinical guideline synthesising BSH 2017–2025 (UK Myeloma Society / UK Myeloma Forum) and EHA-EMN 2025, anchored in NICE NG35 and current NICE technology appraisals. International diagnostic and response frameworks (IMWG 2014, IMWG 2021 PCL, EMN, EHA-EMN 2025) are used for criteria, staging, response assessment and wider context. Version 0.4.1 GOVERNANCE POLISH — May 2026.

Document code: MHA-MYELOMA-2026-v0.4.1-GOVERNANCE-POLISH    Division: Haematological Malignancy    Current version: May 2026 (governance-polish draft)    Review due: Before any deployment — consultant and pharmacy sign-off; then May 2027 or sooner on NICE / BSH / UKMS / EHA-EMN update.

1Scope and Purpose

This page covers the diagnosis, monitoring and management of plasma cell disorders in adults aged ≥18 years across the full disease continuum, integrating BSH and UK Myeloma Society / UK Myeloma Forum recommendations with NICE technology appraisals, NICE NG35 and EHA-EMN 2025 evidence-based guidelines. It applies in outpatient haematology, day-case and inpatient settings, and in shared-care pathways with nephrology, palliative care, transplant centres and approved cellular-therapy centres.

Primary plasma cell leukaemia, AL amyloidosis and Waldenström macroglobulinaemia are biologically related but follow separate UK pathways and are signposted only.

1ANICE Horizon Scanning: Recently Approved, In-Development and Evolving Myeloma Therapies

This section separates therapies by their current NICE classification: routinely recommended; managed-access / Cancer Drugs Fund; in development; awaiting development; discontinued or terminated; and off-label, specialist-centre or trial-only. Entries are listed in order of pathway position (frontline → maintenance → relapse → cellular therapy → biomarker-restricted).

2Clinical Overview and Epidemiology

Plasma cell disorders form a biological continuum from monoclonal gammopathy of undetermined significance (MGUS), through smouldering multiple myeloma (SMM), to symptomatic multiple myeloma (MM), plasma cell leukaemia (PCL) and related lymphoplasmacytic malignancies. The same clonal genetic events are detectable across these states, with progressive acquisition of secondary copy-number changes and single-nucleotide variants as disease evolves.

Myeloma accounts for approximately 2% of all cancers in the UK and is the second most common haematological malignancy. Median age at diagnosis is 70 years, with a slight male predominance. Five-year survival has more than doubled over the past two decades with sequential approval of proteasome inhibitors, immunomodulatory agents, anti-CD38 monoclonal antibodies and, most recently, T-cell-redirecting therapies. Cure remains uncommon outside selected high-risk transplant strategies and clinical trials, so the standard framing is one of sustained disease control rather than eradication.

Two parallel concepts now sit alongside the traditional diagnostic boundaries. Monoclonal gammopathy of clinical significance (MGCS) captures patients in whom a small clone causes organ injury without meeting criteria for haematological malignancy. Monoclonal gammopathy of renal significance (MGRS) is the renal subset of MGCS and is addressed in its own section.

Defining the entities — IMWG 2014 framework

Source: Rajkumar 2014 (Lancet Oncol); Fernández de Larrea 2021 (Blood Cancer J).

SLiM CRAB — Myeloma-defining events

Source: Rajkumar 2014; reproduced in Hughes 2024 BSH Good Practice Paper.

3Guideline Basis (Methodology)

This page integrates UK, European and international evidence frameworks. Each recommendation is tagged with its source society and (where available) evidence grade. UK clinical practice statements are drawn from BSH/UKMS/UKMF and NICE; European context is drawn from EHA-EMN 2025; international diagnostic and response criteria are drawn from IMWG.

P — Population

Adults (≥18 years) with confirmed MGUS, SMM, MGRS, NDMM (transplant-eligible or ineligible), high-risk myeloma, or relapsed/refractory disease.

I — Intervention

Surveillance protocols; proteasome inhibitors (bortezomib, carfilzomib, ixazomib); immunomodulatory agents (lenalidomide, pomalidomide, thalidomide); anti-CD38 monoclonal antibodies (daratumumab, isatuximab); high-dose melphalan and ASCT; BCMA-directed T-cell engagers (teclistamab, elranatamab, linvoseltamab); GPRC5D T-cell engager (talquetamab); BCMA CAR-T (ide-cel, cilta-cel); BCL2 inhibitor in t(11;14) (venetoclax, off-label in UK); selective inhibitor of nuclear export (selinexor); BCMA antibody-drug conjugate (belantamab mafodotin).

C — Comparator

Alternative regimens within or across drug classes; clinical trial enrolment; supportive care alone in selected late-line patients.

O — Outcomes

Progression-free survival, overall survival, MRD-negativity (10⁻⁵ and 10⁻⁶), overall response rate, treatment-related mortality, infection rate, quality of life, treatment-free interval.

Source societies and frameworks

• BSH and UK Myeloma Society / UK Myeloma Forum — UK national guideline framework; primary driver for UK practice (Snowden 2017, Sive 2021, Stern 2023, Hughes 2024, two Kaiser 2024 papers, Pinney 2025, Jenner 2025).
• NICE — NG35 (diagnosis and management) and the individual technology appraisals listed in Section 1.
• EHA-EMN 2025 — European Hematology Association / European Myeloma Network evidence-based guideline (Dimopoulos 2025, Nat Rev Clin Oncol). Replaces EHA-ESMO 2021.
• IMWG — 2014 diagnostic criteria (Rajkumar), 2020 risk model for SMM (Mateos), 2021 PCL redefinition (Fernández de Larrea).
• IKMG 2019 — International Kidney and Monoclonal Gammopathy Research Group consensus on MGRS (Leung).

Evidence grading

• High — RCTs or meta-analyses with consistent results.
• Moderate — RCTs with limitations or observational data with a strong effect size.
• Low — Observational or indirect evidence.
• Very low — Case series or expert opinion.

4The Plasma Cell Disease Continuum

The boundary between MGUS, SMM and active myeloma is biological rather than absolute. Disease moves along the continuum at a rate that varies with clonal burden, cytogenetic features and host factors. A consistent monitoring framework, with timely transitions in care intensity, prevents both overtreatment and missed progression.

Sources: Stern 2023 BSH MGUS; Hughes 2024 BSH SMM; Lakshman 2018; Mateos 2020.

5MGUS — Investigation and Risk Stratification

MGUS is defined by a serum M-protein < 30 g/L, clonal bone marrow plasma cells < 10%, and the absence of any feature of myeloma or a related lymphoplasmacytic malignancy. Prevalence is approximately 3% over the age of 50 and rises with age. Most patients die of unrelated causes. The average risk of progression to a related malignancy is approximately 1% per year and persists beyond 25 years. IgM MGUS is more likely to progress to lymphoplasmacytic lymphoma or Waldenström macroglobulinaemia than to myeloma.

Initial investigations (all patients)

• FBC, urea and electrolytes, eGFR, corrected calcium, albumin.
• Urine dipstick for proteinuria; if positive, send urine protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR).
• Serum protein electrophoresis with quantification of the M-protein and uninvolved immunoglobulins.
• Immunofixation to confirm M-protein type.
• Serum free light chain assay (kappa, lambda, ratio).
• Serum LDH and β2-microglobulin only if myeloma is suspected.

Serum FLC testing is central to assessment. Routine 24-hour urine collection is not required for initial screening in most UK pathways. Urine studies remain important where local laboratory protocols, amyloid/MGRS assessment, response assessment or trial requirements specify them.

Mayo Clinic risk stratification — preferred UK model

The 2005 Mayo Clinic model uses three readily available variables: an abnormal kappa:lambda FLC ratio (< 0.26 or > 1.65), a serum M-protein > 15 g/L, and a non-IgG isotype (IgA or IgM). Patients are stratified by the number of risk factors present.

Source: Rajkumar 2005 (Blood); endorsed by Stern 2023 BSH Good Practice Paper.

BSH 2023 recommends a model that does not require bone marrow biopsy. Alternative models (Spanish PETHEMA, Swedish four-factor with immunoparesis, IMWG) have not been compared head-to-head with the Mayo model and remain supplementary in UK practice.

Bone marrow and imaging — risk-stratified

• Low and low-intermediate risk MGUS: no bone marrow examination and no imaging at diagnosis.
• High-intermediate and high-risk MGUS: bone marrow aspirate, trephine, plasma cell immunophenotyping and FISH; whole-body imaging (low-dose WB-CT, WB-MRI or PET-CT, by clinical question and local access).
• At the high-intermediate or high-risk threshold, also send urine ACR, troponin and NT-proBNP to screen for AL amyloidosis.

Monitoring schedule

• All newly diagnosed MGUS: repeat FBC, creatinine, calcium, M-protein and serum FLC at 6 months.
• Low-risk MGUS: annually thereafter; consider longer intervals or discharge to primary care where life expectancy is short.
• Low-intermediate MGUS: annual review in primary or secondary care.
• High-intermediate and high-risk MGUS: annual secondary-care review (virtual or face-to-face). Re-stratify formally every 3 years.
• Any progressive rise in M-protein or FLC, or development of anaemia, ESR rise, renal impairment, hypercalcaemia or new bone pain, prompts urgent reassessment.

BSH 2023 recommendations

• Risk-stratify all newly diagnosed MGUS using a validated published model that does not require bone marrow biopsy (Mayo criteria preferred).
• Low and low-intermediate risk MGUS do not need bone marrow examination or imaging at diagnosis.
• High-intermediate and high-risk MGUS need bone marrow examination and whole-body imaging.
• Decisions to treat MGCS with systemic chemotherapy must be made through an MDT with appropriate sub-specialty representation.
• Clear information and psychological support at diagnosis and at each review.

MGCS — monoclonal gammopathy of clinical significance

MGCS describes organ damage from a small B-cell or plasma cell clone where criteria for haematological malignancy are not met. Recognised entities include scleromyxoedema, IgM-associated peripheral neuropathy, cold agglutinin disease, POEMS syndrome, Schnitzler syndrome, type 2 mixed cryoglobulinaemia and capillary leak syndrome. Management is sub-specialty led with MDT input.

Other MGUS-associated risks

• Increased risk of axial fractures; optimise vitamin D and calcium; consider DEXA in patients with additional osteoporosis risk factors.
• Modestly increased risk of venous (and to a lesser extent arterial) thrombosis; routine primary thromboprophylaxis is not recommended.
• Increased risk of bacterial infection; ensure vaccination is current.
• Psychological burden of watch-and-wait should be acknowledged and supported at each visit.

6Smouldering Myeloma — Diagnosis, Risk and Monitoring

Smouldering myeloma sits between MGUS and active myeloma. Untreated, the rate of progression to symptomatic myeloma is approximately 10% per year in the first five years, 3% per year for the next five years, and 1% per year thereafter. The risk varies widely with biological behaviour and is best estimated using a validated model.

Diagnostic criteria (IMWG 2014)

• Serum M-protein ≥ 30 g/L, or urinary M-protein ≥ 500 mg/24 h, and/or clonal bone marrow plasma cells 10–59%.
• Absence of myeloma-defining events (SLiM CRAB) and no amyloidosis.

Investigations at diagnosis

Source: Hughes 2024 BSH Good Practice Paper; cross-referenced with Sive 2021 BSH/UKMF guideline.

Risk stratification — Mayo 20-2-20 and IMWG 2020

BSH 2024 endorses the Mayo 20-2-20 (2018) and the updated IMWG 2020 model that incorporates FISH.

Source: Lakshman 2018 (Blood Cancer J); endorsed by Hughes 2024.

Re-stratify patients annually for the first five years post-diagnosis. Movement to a higher risk group between assessments is itself prognostic.

Monitoring and intervention

• Low-risk SMM: 3-monthly clinical and biochemical review for the first year, extending to 6–12 monthly if stable.
• Intermediate-risk SMM: 3-monthly review for 1–2 years, extending to 4–6 monthly if stable.
• High-risk SMM: 3-monthly review for at least 5 years; consider entry into a clinical trial. Outside trials, BSH 2024 states there is insufficient evidence to treat SMM routinely.
• Repeat imaging annually in high-risk SMM and at a low threshold in those with evolving disease markers. Equivocal or solitary focal lesions at baseline warrant interval imaging at 3–6 months.
• QuiRedex and SWOG E3A06 showed benefit from early lenalidomide-based therapy in high-risk SMM. Treatment of SMM is not NHS standard of care outside trials at the time of this draft.

Supportive care in SMM

• Annual flu vaccination, full COVID-19 schedule, conjugate pneumococcal (PCV13) followed by polysaccharide (PPV23) at 2 months, repeated 5-yearly. Functional antibody check at 6 weeks in patients with recurrent infection.
• Recombinant zoster vaccine (Shingrix) two-dose schedule in patients over 50 years.
• No routine VTE prophylaxis. No routine bisphosphonates outside osteoporosis indication.
• Psychological support and clear information at diagnosis and at each review.

7MGRS — Monoclonal Gammopathy of Renal Significance

MGRS describes any kidney disease caused directly or indirectly by a small B-cell or plasma cell clone that does not meet WHO criteria for haematological neoplasm. Diagnosis links the underlying clone to a defined renal lesion confirmed on biopsy. The most common MGRS-associated disorder in the UK is AL amyloidosis. Progression to end-stage kidney disease (ESKD) is common; outcome is determined primarily by depth of haematological response.

Screening in haematology clinic

• All patients with a known MGUS should have serum creatinine, eGFR, urinalysis and urine ACR (not PCR) checked at first presentation.
• Urine dipstick is insensitive to light chains; do not use it to exclude light-chain proteinuria.
• Refer to nephrology if ACR > 30 mg/mmol with a detectable clone, microscopic haematuria, or eGFR declines by more than 25% in 12 months.

Histological classification (IKMG)

Source: Pinney 2025 BSH Good Practice Paper; IKMG consensus (Leung 2019, Nat Rev Nephrol).

Diagnostic workup

• Renal biopsy with light microscopy, immunofluorescence on frozen tissue, electron microscopy, Congo red and where indicated DNAJB9 and protease-digested immunofluorescence. Biopsies should be reported using the Mayo Clinic / Renal Pathology Society standardised report.
• Full haematological workup with bone marrow aspirate and trephine, CD138 and CD20 immunohistochemistry, flow cytometry and FISH for plasma cell or B-cell clones.
• Imaging: WB-MRI or PET-CT for plasma cell clones; CT neck, thorax, abdomen and pelvis (and lymph node biopsy where indicated) for B-cell clones.
• Discussion at a specialist joint haematology and nephrology MDT with renal pathology input.

Principles of treatment

• Aim for the deepest haematological response possible; achieving at least VGPR is associated with better renal outcomes.
• AL amyloidosis follows the separate BSH AL amyloidosis guideline pathway.
• Treatment of the underlying clone is recommended in patients at risk of declining renal function at all stages of CKD to prevent progression to ESKD (eGFR < 15 mL/min/1.73 m²).
• In patients already at ESKD with no extra-renal disease, treatment is reserved for those eligible for renal transplantation; aim for at least VGPR before listing.
• Consider autologous stem cell transplantation in suitable patients who have not achieved CR.
• Long-term joint nephrology and haematology follow-up; lifelong monitoring after treatment completion.

General supportive care in MGRS

8Newly Diagnosed Myeloma — Diagnosis and Workup

Diagnosis follows the IMWG 2014 criteria: clonal bone marrow plasma cells ≥ 10% (or biopsy-proven plasmacytoma) plus one or more myeloma-defining events (SLiM CRAB). Workup is governed in UK practice by the BSH/UKMF 2021 guideline (Sive 2021) and updated for high-risk disease by Kaiser 2024.

Baseline assessment

• Full history including bone pain, fatigue, infection, neuropathy, autonomic and amyloid symptoms; performance status; geriatric assessment in patients aged 75 years or over.
• FBC, U&E, calcium, albumin, LDH, β2-microglobulin, immunoglobulins, SPE, immunofixation, serum FLC, urine ACR.
• Bone marrow aspirate and trephine with plasma cell phenotyping and FISH on CD138-selected cells.
• Cross-sectional imaging by WB-MRI (preferred) or PET-CT. Low-dose WB-CT may be used where appropriate for cortical bone assessment or where WB-MRI/PET-CT is unavailable or unsuitable. Plain skeletal survey should not be used as the sole standard staging investigation where modern whole-body imaging is available.
• Troponin, NT-proBNP, urine ACR and consideration of subcutaneous fat or organ biopsy if amyloidosis is suspected.
• All new diagnoses discussed at a specialist myeloma MDT.

Staging — ISS, R-ISS and R2-ISS

References: Greipp 2005 (JCO); Palumbo 2015 (JCO); D'Agostino 2022 (JCO).

Cytogenetic and molecular profiling (BSH 2024)

BSH 2024 recommends extended cytogenetic profiling at diagnosis in all NDMM patients. Test the complete set: t(4;14), t(14;16), t(14;20), del(1p), gain(1q) and del(17p) by FISH or equivalent validated molecular methods. Where technically feasible, results should be available within four weeks of an adequate first bone marrow sample and a maximum of eight weeks if repeat biopsy is required. Gene expression profiling (for example SKY92) identifies an additional approximately 10% of high-risk patients not detected by FISH alone.

Standard-risk transplant-eligible NDMM — UK NHS framework

Standard UK NHS induction has been a bortezomib-based triplet (most commonly VTd or VCd) followed by ASCT with melphalan 200 mg/m² conditioning and lenalidomide maintenance until progression (TA680). Daratumumab-containing quadruplet induction is increasingly used in line with the CASSIOPEIA evidence base and current NICE technology appraisals. The current NICE-commissioned quadruplet for the transplant-eligible setting is D-VTd (TA763, within NICE criteria). D-VRd (PERSEUS-based) is the subject of an in-development NICE appraisal under identifier GID-TA10726 / ID3843 (the v0.3 draft incorrectly cited TA11254 — corrected in v0.4); the cited NICE in-development reference relates to transplant-unsuitable NDMM, not transplant-eligible disease. D-VRd should be treated as horizon/evidence content only for the TE-NDMM pathway pending final NICE guidance and verified pathway placement.

Maintenance after ASCT

Transplant-ineligible NDMM

9High-Risk and Transplant-Eligible NDMM

Approximately 25% of transplant-eligible patients experience early relapse after high-dose melphalan and ASCT. These patients have substantially shortened overall survival and are now defined by molecular features.

Molecular definition (BSH 2024)

• Two or more high-risk cytogenetic abnormalities (2+ HRCA, also called double-hit): any pair drawn from t(4;14), t(14;16), t(14;20), del(1p), gain(1q) and del(17p).
• SKY92 GEP high-risk signature (an additional approximately 10% of HRMM).
• Primary plasma cell leukaemia (≥ 5% circulating plasma cells, IMWG 2021 redefinition).
• Extramedullary disease at diagnosis is associated with HRCA and a high-risk gene expression profile.

Stratified treatment evidence base

Source: Kaiser 2024 BSH/UKMS Good Practice Paper.

UK practice points

• Current NHS England standard for high-risk NDMM is single ASCT; tandem ASCT is recommended in EHA-EMN and is the only HRMM-specific intensification routinely available on the NHS, based on the EMN02 subgroup analysis. BSH 2024 notes that tandem ASCT carries cumulative toxicity and quality-of-life burden.
• Where access permits, treatment as per OPTIMUM, CONCEPT, IFM 2018-04 or EMN12 should be considered.
• Tandem ASCT may be considered for HRMM when extended intensified consolidation and maintenance are not available.
• Toxicities should be monitored closely with early dose reduction rather than discontinuation of multi-target combinations.
• Subcutaneous and home-administered supportive treatments should be used where safe.

10Imaging Across the Pathway

Whole-body MRI with diffusion weighting (WB-MRI), FDG PET-CT and low-dose whole-body CT all have defined roles in modern myeloma pathways. WB-MRI and PET-CT can detect marrow or extramedullary disease before cortical bone destruction, while CT remains useful for cortical bone assessment and fracture risk. NICE NG35 recommends modern whole-body imaging at diagnosis; local pathways should specify the first-line modality according to access, clinical question and reporting expertise.

Indications for advanced imaging

Source: Kaiser 2024 BSH/UKMS advanced imaging paper; NICE NG35.

Imaging not recommended

• Skeletal X-ray survey should not be used as the sole standard assessment where modern whole-body imaging is available.
• Axial MRI alone is less complete than WB-MRI and may miss extra-axial disease; reserve it for focused clinical questions such as suspected cord compression or local symptoms.
• At relapse, imaging should be matched to the clinical question. Where extramedullary, oligo-secretory or non-secretory progression is suspected, WB-MRI or PET-CT should be considered rather than relying only on cortical bone imaging.

11Relapsed and Refractory Myeloma

Definitions follow IMWG and BSH/UKMS 2025. Relapsed myeloma (RMM) describes serological or clinical progression in patients who had a minimal response or better. Relapsed and refractory myeloma (RRMM) describes progression on treatment or within 60 days of completing the last therapy. Triple-class refractory myeloma is refractoriness to at least one IMiD, one PI and one anti-CD38 monoclonal antibody. Penta-refractory myeloma is refractoriness to two IMiDs, two PIs and an anti-CD38 antibody.

Evaluation at progression

• Repeat FBC, U&E, calcium, LDH, β2-microglobulin, immunoglobulins, SPE, immunofixation and serum FLC.
• Bone marrow aspirate and trephine, particularly at first or second relapse, to characterise the clone and exclude myelodysplasia. Repeat FISH where genomic information may direct therapy (for example t(11;14) for venetoclax).
• Functional cross-sectional imaging (WB-MRI or PET-CT) for new bone symptoms, oligo-secretory or extramedullary disease. Plain X-ray is inadequate.
• Full reassessment of patient-specific factors: previous response, toxicities, performance status, frailty, comorbidity, preference and trial eligibility.

Asymptomatic biochemical relapse

• Slow progression without CRAB criteria can be monitored initially every month.
• A rapid trajectory of biochemical progression, high-risk features, prior short treatment-free interval, light chain renal injury, extramedullary disease or unfavourable cytogenetics support earlier treatment initiation.

Principles of treatment selection (BSH/UKMS 2025)

• Triplet regimens are recommended over doublets, subject to tolerance (Strong / High).
• Generally use a PI–IMiD–steroid combination (carfilzomib–lenalidomide–dexamethasone; ixazomib–lenalidomide–dexamethasone; pomalidomide–bortezomib–dexamethasone).
• Switch backbone agent from the most recent regimen unless there has been a long treatment-free interval.
• When a PI doublet is used, carfilzomib–dexamethasone is preferred to bortezomib–dexamethasone.
• When an IMiD doublet is used, lenalidomide–dexamethasone or pomalidomide–dexamethasone are options.
• Use risk-adapted thromboprophylaxis with all IMiDs and varicella zoster prophylaxis with proteasome inhibitors.
• Restart bisphosphonates at frank relapse if previously stopped.
• Clinical trial enrolment should be considered at every line of therapy, including in multiply-relapsed patients.

UK-relevant regimens at relapse

Second autologous stem cell transplant

• Consider second ASCT in suitable patients who have achieved at least PR with reinduction.
• Outcomes are less favourable in the presence of high-risk cytogenetics; repeat FISH at relapse is recommended where second ASCT is being considered.
• Melphalan 200 mg/m² remains the standard conditioning regimen.
• Collect sufficient stem cells at first mobilisation for two transplants where feasible.

Response assessment

Source: IMWG response criteria, Kumar 2016 (Lancet Oncol); EHA-EMN 2025.

12Supportive Care and Survivorship

Survival in myeloma has improved substantially over the past two decades. Cumulative burden of disease and treatment now drives a survivorship agenda alongside relapse management. The BSH 2017 guideline on late and long-term consequences (Snowden 2017) remains the UK reference and should be read alongside NICE NG35 and the BSH supportive care framework.

Infection and immunity

• Infection is a major cause of morbidity and mortality in myeloma. Immunosuppression is greatest at diagnosis, during aggressive relapse and in heavily pre-treated disease.
• Routine antibacterial prophylaxis is not recommended at every stage; consider prophylactic antibiotics in selected high-risk windows.
• Offer antiviral prophylaxis (aciclovir or valaciclovir) with proteasome inhibitor-based treatment until at least six weeks after stopping. Consider lifelong prophylaxis in patients with previous shingles.
• Consider IVIg replacement based on infection history, hypogammaglobulinaemia, comorbidities and vaccine response, in line with NHS England immunoglobulin guidance.
• Avoid live attenuated vaccines (BCG, MMR, oral typhoid, yellow fever, varicella zoster live vaccine). Use Shingrix (recombinant zoster vaccine) for shingles protection.
• Annual influenza and full COVID-19 vaccination schedules for patients and household contacts.
• PCV13 followed by PPV23 at 2 months, repeated 5-yearly; Hib vaccination should also be considered.

Bone health and pain

• Bisphosphonates (zoledronic acid or pamidronate) for all newly diagnosed patients requiring treatment, regardless of demonstrable bone lesions.
• Restart bisphosphonates at frank relapse if previously stopped.
• Optimise calcium and vitamin D; consider DEXA in patients with additional osteoporosis risk factors.
• Maintain dental review and consider osteonecrosis of the jaw risk; assess before initiating bisphosphonates.
• Active pain management including neuropathic pain control with gabapentin or pregabalin; refer to pain specialist where indicated.

Renal, cardiovascular and metabolic

• Routine monitoring of eGFR and urine ACR; protect renal function.
• Annual cardiovascular risk assessment including blood pressure, HbA1c and lipid profile.
• NT-proBNP or BNP as a screening tool for cardiac amyloidosis or other cardiac dysfunction; echocardiography and specialist referral if elevated.
• Awareness of metabolic syndrome, sarcopenic obesity and steroid-related complications. Encourage tailored physical activity programmes.

Endocrine, neurological and other late effects

• Annual screening for hypothyroidism and hypogonadism, particularly post-HSCT.
• Screen patients with peripheral neuropathy for vitamin B12 deficiency, diabetes and renal causes.
• Annual ophthalmic screening for cataract and steroid-related eye disease. Belantamab patients have specific ophthalmology pathway.
• Consider second primary malignancies (especially AML and MDS) in unexplained or worsening cytopenias.
• Maintain oral and dental hygiene; refer for management of treatment-related dryness, taste change and candidiasis.

Psychosocial and rehabilitation

• Routine holistic needs assessment at diagnosis and at the start and end of each line of therapy.
• Address fatigue, fear of recurrence and coping with watch-and-wait in MGUS and SMM.
• Engage specialist nursing, physiotherapy, occupational therapy and palliative care input appropriate to the stage of disease.
• Signpost to UK patient organisations including Myeloma UK.

Frailty assessment in older patients

Consider baseline geriatric assessment in patients aged 75 years or over and any patient with apparent frailty. The IMWG frailty score (age, comorbidity, geriatric assessment) is simple to apply and correlates with severe toxicity. Use the result to guide treatment intensity, dose reductions and supportive care.

13Audit and Governance

The following audit standards derive from BSH 2023 (MGUS), BSH 2024 (SMM) and BSH/UKMS 2024–2025 (NDMM, high-risk, imaging and relapse). They support trust-level governance and a structured framework for service improvement.

MGUS audit standards (BSH 2023 derived)

SMM audit standards (BSH 2024 derived)

NDMM and relapsed-disease audit standards (BSH/UKMS 2024–2025 derived)

Local implementation checklist (MHA-suggested)

• Confirm pathway for laboratory flagging of new M-proteins and abnormal SFLC ratios.
• Define risk stratification responsibility (primary versus secondary care) and document in local guideline.
• Establish virtual clinic capacity for high-intermediate and high-risk MGUS monitoring.
• Confirm imaging capacity for WB-MRI and PET-CT; pathway for repeat imaging in evolving SMM and at biochemical relapse.
• Local cytogenetic and FISH turnaround times benchmarked against the BSH 2024 four-week target (eight weeks if repeat biopsy required).
• MDT structure with renal, cardiology and amyloidosis input where MGRS or amyloidosis is identified.
• Bispecific and CAR-T pathway: referral route, bridging therapy, supportive care, IVIg, infection prophylaxis.
• Survivorship and holistic needs assessment integrated into routine follow-up.
• Annual audit cycle against the BSH 2023 MGUS, BSH 2024 SMM and BSH/UKMS 2024–2025 NDMM/imaging/relapse audit templates.

UK-anchored treatment and commissioning statement

All treatment principles on this page are anchored in BSH and UKMF / UK Myeloma Society guidance, NICE NG35 and current NICE technology appraisal status where explicitly verified. International diagnostic and response frameworks (IMWG, EHA-EMN 2025) are used for criteria, staging, response assessment and wider context. Where international and UK guidance differ, UK guidance, NHS commissioning and local MDT policy prevail.

Limitations and update plan

• This is an educational summary and does not replace specialist MDT decision making, current NICE technology appraisals, NHS England commissioning criteria or local trust protocols.
• NICE TA numbers cited here are valid as of May 2026; verification against the live NICE register is required before each review cycle and before any prescribing decision.
• Several relevant appraisals remain in development: GID-TA10726 / ID3843 (D-VRd), TA11465 (isatuximab combinations induction), GID-TA10905 / ID4012 (cilta-cel earlier-line), GID-TA11846 / ID6639 (isatuximab maintenance). Ixazomib maintenance (GID-TA10843 / ID1517) was discontinued at NICE in February 2026. This page will be updated when relevant guidance is published.
• Belantamab combination access is in re-evaluation; verify current status.
• Cilta-cel access in routine commissioning is currently limited (TA889 terminated); this may change with the in-development earlier-line appraisal.
• Venetoclax for t(11;14) is not NICE-commissioned for myeloma and is presented as off-label / specialist-centre use only.
• Update schedule: review in May 2027 or sooner on relevant NICE, BSH/UKMS or EHA-EMN updates.

Pre-publication governance checklist (must be cleared before live deployment)

• Live NICE TA verification completed for every named regimen.
• Blueteq form requirements / NHS England commissioning status checked for every regimen presented as available.
• Regimen access statements (routine, managed-access, in-development, terminated, off-label) checked by consultant haematologist and pharmacist before sign-off.
• Doses checked against current SmPC, local Trust e-prescribing protocols and renal/hepatic adjustment rules. Dose blocks remain marked as educational only.
• Algorithm asset links (HTML to JPEG / SVG) verified — no broken links to assets that are not present in the repository.
• Quick-ref card and full guideline cross-checked for consistency on TA numbers, line of therapy, and regimen access.
• References checked for DOI, PMID and year accuracy.
• NICE horizon-scanning section (Section 1A) re-checked against live NICE pages immediately before deployment.
• Distinction confirmed between currently recommended (TA763, TA587, TA1098, TA680, TA695, TA1015, TA1114, TA1133 and others), managed-access (TA1023 elranatamab), in-development (GID-TA10726 / ID3843 D-VRd; GID-TA10905 / ID4012 cilta-cel earlier line; GID-TA11846 / ID6639 isatuximab maintenance), discontinued (GID-TA10843 / ID1517 ixazomib maintenance) and terminated (TA889 cilta-cel) appraisals.
• D-VRd identifier confirmed as GID-TA10726 / ID3843 unless NICE has since issued final TA guidance with a new TA number — replace throughout if updated.
• Cilta-cel TA889 (terminated) and GID-TA10905 / ID4012 (in development, earlier line) kept separate in every reference throughout the document.
• Ixazomib maintenance GID-TA10843 / ID1517 labelled discontinued (Feb 2026), not in development, in every reference throughout the document.
• Page layout, sidebar, evidence badges and download links match the live MHA malignant guideline framework (CLL page v1.9 as reference).
• Quick-ref card carries the safety footer on every page; dose blocks within it carry the dose-example caveat.
• Pharmacy review of thromboprophylaxis, antiviral prophylaxis, antimicrobial prophylaxis, IVIg, steroid toxicity mitigation and renal dose-adjustment language confirmed.
• The draft label removed only after consultant review, pharmacy review, NICE TA re-verification and approved-centre confirmation are complete.

14References

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