On the last day of the 14th International Myeloma Workshop in Kyoto, Japan, the issue of how to manage relapsed multiple myeloma was addressed.

What is the correct sequence of therapy in the treatment of relapsed multiple myeloma?

During the past 10 years the life expectancy of multiple myeloma (MM) patients has doubled with the use of thalidomide, lenalidomide and bortezomib. All of these drugs have demonstrated efficacy in the treatment of relapsed and relapsed/refractory patients. Since these agents are frequently used as part of frontline regimens, defining the correct sequence of their use in the treatment of relapsed MM can be a challenge.

The choice of novel agents will depend on disease-related, patient-related or treatment-related factors, and the choices are often predicted by the history of prior drug exposure.

Bortezomib-based salvage therapy is optimal for patients who have relapsed disease after immunomodulatory therapy or who have high risk genetics and/or renal impairment. Lenalidomide-based salvage therapy is preferable for patients with prior exposure to bortezomib, patients with significant neuropathy and those with good risk cytogenetics. Thalidomide-based salvage therapy is preferable for patients presenting with cytopenia, severe renal impairment and in those who have had prior exposure to bortezomib and/or lenalidomide.

When should therapy be started in relapsed patients with multiple myeloma?

Instead of a 'one size fits all' approach to therapy, an individualised treatment plan should be agreed for each relapsed patient. Evidence of new bone lesions or extramedullary manifestations should be sought.

This is ideally done with the use of PET/CT or whole body MRI. A bone marrow biopsy can confirm if there has been disruption of the correlation between M-component level and clonal size, or a light chain escape is suspected.

In the case of no new abnormalities, treatment can be temporarily withheld in patients with a favourable prognosis, but close monitoring is required. In patients with a history of aggressive disease or light chain induced renal failure, del17p, t(4:14), high LDH and/or plasmablastic morphology, initiation of treatment seems warranted even in the absence of signs of disease progression. In patients with slowly evolving M-component, treatment should be withheld until the emergence of early signs of myeloma-associated organ damage occurs.

Therapy is indicated in cases of clear signs of clinical progression and/or imminent complications.