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Case history

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Image not available. A previously fit 58-year-old man presented with fatigue and back pain. Investigations revealed an immunoglobulin G (IgG) λ paraprotein level of 31 g/l and immune paresis, albumin 30 g/l, β2-microglobulin 2.9 mg/l, and normal full blood count, renal function and serum free light chains. A skeletal survey showed vertebral collapse at T1. A bone marrow biopsy identified a 70% infiltrate with plasma cells, confirming a diagnosis of International Staging System (ISS) stage 2 multiple myeloma. Cytogenetics at diagnosis was not available.

He was commenced on cyclophosphamide, thalidomide and dexamethasone, together with bisphosphonates. He achieved a partial response after six cycles. His treatment was consolidated with high-dose melphalan (200 mg/m2) and an autologous stem cell transplant (ASCT). Bone marrow biopsy on day 100 showed no excess of plasma cells and a drop in paraprotein level to 3 g/l, confirming a very good partial response.

His paraprotein level started rising 13 months after ASCT. A bone marrow biopsy showed 46% plasma cells with deletion 17p and translocation t(4;14) identified by interphase fluorescence in situ hybridization (FISH). He completed four cycles of bortezomib, doxorubicin and dexamethasone induction treatment and achieved a partial response; his paraprotein level dropped from 23.6 to 4.3 g/l. He had a second ASCT in July 2012, achieving a second very good partial response (paraprotein nadir 1.4 g/l)

Serological progression occurred 10 months after the second ASCT, and he was commenced on ixazomib, lenalidomide and dexamethasone. His paraprotein level dropped from a peak of 25 g/l to a nadir of 9.9 g/l following two cycles of treatment. He had 26 cycles in total until there was clear progression with symptomatic anaemia and a paraprotein level of 67 g/l. He had 60% plasma cells in his bone marrow and the same cytogenetic changes.

He was then commenced on pomalidomide, carfilzomib and dexamethasone and responded well: his anaemia resolved and his paraprotein level dropped to 10.3 g/l after four cycles. Therapy is ongoing.

When is treatment indicated in myeloma?

What constitutes high-risk multiple myeloma?

Can adverse prognostic markers be overcome using existing therapies?

What is the evidence for a second ASCT?

What is the current evidence for ixazomib combinations?

What is the efficacy of carfilzomib and pomalidomide in multiply relapsed myeloma?

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When is treatment indicated in myeloma?

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The International Myeloma Working Group has defined criteria for monoclonal gammopathy of undetermined significance and for asymptomatic and symptomatic myeloma. Patients with symptomatic myeloma have evidence of myeloma-related organ and tissue impairment and they require treatment. The definition of symptomatic myeloma was updated in 2014 to recommend that patients with clonal bone marrow plasma cells ≥60%, serum free light chain ratio ≥100, or more than one focal lesion on MRI studies be included in the definition of myeloma-defining events.1 These were introduced as each of these markers has been demonstrated in independent studies to confer a risk of developing related organ and tissue impairment ...

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