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04-01-2016 | Treatment | Article

Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity

R F Cornell, A A Kassim


The use of modern therapies such as thalidomide, bortezomib and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM). However, patients with relapsed/refractory multiple myeloma (RRMM) often have poorer clinical outcomes and might benefit from novel therapeutic strategies. Emerging therapies, such as deacetylase inhibitors, monoclonal antibodies and new proteasome inhibitors, appear promising and may change the therapeutic landscape in RRMM. A limited number of studies has shown a benefit with salvage ASCT in patients with RRMM, although there remains ongoing debate about its timing and effectiveness. Improvement in transplant outcomes has re-ignited a debate on the timing and possible role for salvage ASCT and allogeneic stem cell transplant in RRMM. As the treatment options for management of patients with RRMM become increasingly complex, physicians must consider both disease- and patient-related factors in choosing the appropriate therapeutic approach, with the goal of improving efficacy while minimizing toxicity.

Bone Marrow Transplant 2016; 51: 479–491. doi: 10.1038/bmt.2015.307

Multiple myeloma (MM) is a clonal B-cell disorder of terminally differentiated plasma cells that accounts for ≈ 10% of hematologic malignancies.1, 2 It is the second most common hematologic malignancy in the United States, with an overall incidence rate of 4.4 cases per 100 000 population/year.3 MM remains largely incurable, thus therapy is initiated when patients are symptomatic with the ultimate goal of improving patients' long-term outcomes.4 Over the past 10–15 years, the introduction of modern therapies, such as immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), has led to significant improvements in overall survival (OS).5 Five-year survival rates have improved, from 34.8% (1998–2001) to 44.6% (2006–2009), in both transplant-eligible and transplant-ineligible patients, primarily due to treatment advancements in newly diagnosed MM (NDMM).6, 7, 8, 9

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