Tailoring Treatment for Multiple Myeloma Patients With Relapsed and Refractory Disease

Responses to treatment of relapsed and refractory multiple myeloma are characteristically short, and median survival is as brief as 6 months. Although prognostic factors in the context of relapsed and refractory disease require further characterization, high-risk patients include those with certain cytogenetic abnormalities, high β2-microglobulin, and low serum albumin. The development of novel therapies targeting disease biology and tumor microenvironment has significantly improved the outlook for patients with relapsed and refractory disease, with bortezomib (Velcade), a first-in-class proteasome inhibitor, and the immunomodulatory agents thalidomide (Thalomid) and lenalidomide (Revlimid) constituting “backbone” agents in this setting. More recent approaches for treating relapsed and refractory myeloma that are recommended by the National Comprehensive Cancer Network include single-agent bortezomib, single-agent lenalidomide, bortezomib/dexamethasone, bortezomib plus pegylated liposomal doxorubicin, lenalidomide/dexamethasone, and lenalidomide/bortezomib/dexamethasone. Individualized treatment of progressive myeloma should take into account the time to progression and/or the type of prior therapy. Additional clinical challenges discussed in this article are renal dysfunction, extramedullary disease, and advanced bone disease. Finally, participation in clinical trials is especially encouraged in this patient population.

Supported by an educational grant from Millennium Pharmaceuticals, Inc.

Survival in multiple myeloma (MM) has improved significantly since 1990,[1] but the disease remains incurable, with most patients responding to therapy but all eventually relapsing. Some have primary refractory disease and do not respond to initial therapy, and those with relapsed and refractory disease constitute a serious and unmet medical need. Overall, the median survival of patients with relapsed and refractory MM is as short as 6 months.[2]

TABLE 1

NCCN-Recommended Salvage Therapies for Multiple Myeloma

Patients who have received at least two prior therapies and have progressed on therapy or within 60 days of last treatment are usually defined as having “relapsed and refractory” MM. Clinical considerations in caring for these patients include the number of prior therapies, existing and potential toxicities related to treatment, and disease characteristics (eg, aggressiveness of relapse, relapsed disease emerging from prior remission vs disease that is truly both relapsed and refractory, and other high-risk features). Features associated with poor prognosis are t(4;14) or t(14;16), deletion of chromosomes 17 and/or 13, hypodiploidy, high β2-microglobulin, and low serum albumin. Additional challenging clinical scenarios include patients with light-chain and immunoglobulin A (IgA) isotype, renal failure, extramedullary disease, hyposecretory myeloma, and/or advanced bone disease.[2]

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