Chapter 5 – Treatment of relapsed multiple myeloma

Contributor: Michel Delforge

1 – General considerations

Despite the therapeutic advances made in the treatment of multiple myeloma (MM) and the subsequent progress in progression-free (PFS) and overall (OS) survival, this disease still remains incurable for the large majority of patients. Cure in myeloma is considered as a relapse-free interval of at least 10–15 years (‘operational cure’) and can be achieved either by full disease eradication, or alternatively by a return to a premalignant indolent monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma status [1]. This percentage of patients never requiring second-line treatment is currently estimated at 10–15% after high-dose therapy [2]. Elderly, and particularly very elderly MM patients, will sometimes never make it to second or later lines of treatment because of intercurrent diseases or death related to other causes [3]. But for the majority of MM patients, their myeloma will behave as a chronic disorder with episodes of remission followed by symptomatic relapses requiring treatment. Whereas the treatment approach in front-line is more uniform throughout the world [4,5], treatment at relapse is more heterogeneous, as therapeutic choices at this stage are not only driven by drug availability, patient status, and disease characteristics, but also by the type of previous treatment(s), their therapeutic effect, and toxicities. Before discussing these different topics in more detail, it should be kept in mind that with each relapse myeloma will become more difficult to treat due to the emergence of resistant clones until the myeloma cells have become totally refractory to any available treatment [6,7].

Moreover, with each treatment course patients tend to become more vulnerable to hematological and non-hematological toxicities. Therefore, particularly at later relapses where there is no standard of care, the benefits and potential risks of therapeutic decisions should be carefully balanced in each individual patient, to minimize excess toxicities. In this chapter we will discuss some general aspects on the approach to the patient with relapsed MM, followed by a more in depth description of the anti-myeloma drugs that are currently available, or will become available in the near future.