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

ABSTRACT: 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.

SUBMITTER: Cornell RF

PROVIDER: S-EPMC4827007 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Cornell R F RF Kassim A A AA

Bone marrow transplantation 20160104 4

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 in ...[more]

PMID: 26726946

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Project description:Background:The refractory/relapsed multiple myeloma (RRMM) remains a big clinical challenge, due to its biological and clinical complexity. Leading hematologists have performed many randomized controlled trials (RCTs) worldwide, and their findings were summarized in a recently published network meta-analysis (NMA) but with certain limitations. Materials and methods:We performed an updated NMA of RCTs related to RRMM treatment, focusing on efficacy measures including the nonresponse rate (NRR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS). The PubMed database was searched. We extended the literature search strategy of a previous NMA to June 30, 2017 and included additional primary RCTs. The surface under the cumulative ranking curve (SUCRA) was calculated to rank the regimens. A weighted-average method was used to rank the regimens by summarizing SUCRAs across different outcome measures. Results:Finally, a total of 24 RCTs were included in this updated NMA. According to the result, the combination of daratumumab, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of NRR, TTP, and PFS (NRR: odds ratio [OR] =0.046, 95% credible interval [CrI] =[0.024, 0.085]; TTP: hazard ratio [HR] =0.14, 95% CrI =[0.092, 0.2]; PFS: HR =0.12, 95% CrI =[0.077, 0.18], compared with dexamethasone singlet). The combination of ixazomib, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of OS (HR =0.30, 95% CrI =[0.17, 0.54], compared with dexamethasone). The combination of daratumumab, lenalidomide, and dexamethasone ranked first in terms of overall efficacy (weighted average of SUCRAs =0.920). Conclusion:The combination of daratumumab, lenalidomide, and dexamethasone may currently be the most effective regimen in the population of RRMM patients. Triplet regimens containing daratumumab, ixazomib, carfilzomib, or elotumumab plus lenalidomide and dexamethasone can be recommended as first-line therapies for RRMM patients.

Dataset Information

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

Publications

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

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