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Case history

image 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?

When is treatment indicated in myeloma?

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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