Multiple Myeloma

Multiple myeloma is a clonal plasma cell malignancy of the bone marrow causing end organ damage (CRAB: hypercalcaemia, renal failure, anaemia, bone lesions).

• Incidence 7 per 100,000, median age 70; 10% of haematological cancers; higher in Black populations.

• Preceded by MGUS and smouldering myeloma.

• Diagnostic criteria (IMWG): 10% or more clonal plasma cells (or biopsy proven plasmacytoma) plus one or more of CRAB, clonal plasma cells 60% or more, involved to uninvolved light chain ratio 100 or more, or more than one focal lesion on MRI.

• Risk stratification: R-ISS/R2-ISS using FISH (t(4;14), t(14;16), del(17p), 1q gain), LDH, beta-2 microglobulin, albumin.

• Complications: bone fractures, cord compression, hyperviscosity, infections, amyloid, renal failure.

• Bone pain (back, ribs), pathological fractures, fatigue, anaemia, recurrent infections, hypercalcaemia (thirst, confusion, constipation), renal failure, neuropathy.

• Spinal cord compression: back pain, weakness, sphincter dysfunction.

• Bleeding, hyperviscosity (rare in IgA).

• Serum protein electrophoresis and immunofixation, serum free light chains, urine electrophoresis, quantitative immunoglobulins.

• Full blood count, calcium, creatinine, albumin, LDH, beta-2 microglobulin.

• Marrow aspirate and biopsy with flow, cytogenetics and FISH.

• Whole body low dose CT or PET-CT; MRI spine/pelvis for smouldering or suspected cord compression.

• Exclude amyloid with fat pad or marrow Congo red.

• Transplant eligible (under 70, fit): induction with daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd) for 4 to 6 cycles; autologous stem cell transplant with melphalan 200 mg/m2; consolidation; lenalidomide maintenance 10 mg daily (15 to 25 mg in selected) until progression; add bortezomib for high risk.

• Transplant ineligible: daratumumab plus lenalidomide and dexamethasone (DRd), or D-VMP/D-VRd lite for 12 to 18 months, then maintenance.

• Typical doses: bortezomib 1.3 mg/m2 SC weekly, lenalidomide 25 mg days 1 to 21, dexamethasone 20 to 40 mg weekly, daratumumab 16 mg/kg weekly then q2 and q4 weeks (SC 1800 mg).

• Relapse: carfilzomib, pomalidomide, isatuximab, selinexor, belantamab; BCMA targeted CAR-T (idecabtagene, ciltacabtagene) and bispecific antibodies (teclistamab, elranatamab, talquetamab).

• Supportive care: zoledronic acid 4 mg IV every 4 weeks for 1 year then every 3 months (or denosumab 120 mg), aciclovir 400 mg twice daily, thromboprophylaxis (aspirin or enoxaparin) with IMiDs, IVIG for recurrent infections, radiotherapy 8 Gy for cord compression or painful lesions, vertebroplasty; dialysis for cast nephropathy.

• Hypercalcaemia: saline, zoledronate, calcitonin, steroids.

• Follow with response assessment (IMWG) and MRD testing.