Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: A meta-analysis of phase III randomized controlled trials
Section snippets
What’s new?
The treatment of RRMM remains a significant clinical challenge worldwide. Currently, whether triplet combination therapy would improve the prognosis of RRMM remains undetermined. The present study demonstrates that triplet regimens result in improved OS, PFS, ORR, VGPR, and CR when compared to doublets, though the risk of grade 3 and 4 adverse events are higher with triplets. The pooled estimates of response and survival strongly favor triplets in the RRMM patients.
Study design
We developed a protocol that defined inclusion criteria, search strategy, outcomes of interest, and analysis plan. The reporting of this systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements (Moher et al., 2009).
Data source
To identify studies for inclusion in our systematic review and meta-analysis, we did a broad search of four databases, including Embase, Medline, the Cochrane Central Register of Controlled Trials, and the Cochrane
Search results
A total of 145 studies were identified from the database search, of which 10 reports were retrieved for full-text evaluation. 135 of which were excluded for the reasons shown in Fig. 1. Finally, a total of 5 RCTs were included. Table 1, Table 2 summarized the baseline and disease characteristics of all included studies. A total of 3179 patients were available for the meta-analysis. According to the inclusion criteria of each trial, patients were required to have an adequate renal, hepatic and
Discussion
Multiple myeloma (MM) is the second most common lymphoid malignancy with 102 826 new cases of MM are diagnosed in 2008 (Ferlay et al., 2010). During the past decades, the introduction of targeted agents such as IMiDs and proteasome inhibitors improves treatment outcomes. However, MM remains incurable and patients eventually relapse (Kumar et al., 2012, Rajkumar, 2011). The prognosis of RRMM patients, particularly those that are refractory to bortezomib and are relapsed from, refractory to or
Funding
None.
Conflicts of interest statement
All authors declare that they have no potential conflicts of interests.
Contributions
Z.S. and F.Z. conceived and designed the experiments. Z. S. and S.W. wrote the main manuscript text. Y. L. and H.G. extracted and analyzed the data: Y.L. and Z.S. prepared the figures; all authors reviewed the manuscript.
Zhiqiang Sun is a medical oncologist (Department of Hematology, Shenzhen Hospital of Southern Medical University). He has interests in the field of novel targeted agents for the treatment refractory or relapsed multiple myeloma.
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2019, Clinical Lymphoma, Myeloma and LeukemiaCitation Excerpt :These studies provide important toxicity and response data to help guide therapy decisions. The major theme from these trials as well as from several meta-analyses is that triplet combinations versus double therapy are generally safe and can improve ORR, PFS, and, in some studies, OS.10,26-39 Thus, the general recommendation is to utilize triplet combinations when appropriate, with goals to improve ORR in order to deepen the response and improve duration of response.
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2019, Clinical TherapeuticsCost-effectiveness of Daratumumab-based Triplet Therapies in Patients With Relapsed or Refractory Multiple Myeloma
2018, Clinical TherapeuticsCitation Excerpt :Up to now, although relapsed or refractory MM (RRMM) remains incurable, patient survival was prolonged significantly due to novel regimens recently approved by the US Food and Drug Administration. In virtue of the outstanding survival outcomes,3 triplet regimens anchored with these novel agents plus traditional regimens are now recommended for RRMM in clinical practice guidelines as standard therapies. According to the latest guidelines, except for elderly or frail patients, almost all patients with RRMM who had received at least 1 or 1 to 3 prior therapies were recommended for the triplet regimens (Table I).4
Zhiqiang Sun is a medical oncologist (Department of Hematology, Shenzhen Hospital of Southern Medical University). He has interests in the field of novel targeted agents for the treatment refractory or relapsed multiple myeloma.