Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: A meta-analysis of phase III randomized controlled trials

Sun, Zhiqiang; Zheng, Fang; Wu, Shao-Guo; Liu, Yanjuan; Guo, Hehe; Liu, Yichen

doi:10.1016/j.critrevonc.2017.03.018

Cited by 26 publications

(16 citation statements)

References 19 publications

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“…This last point is a key difference between this study and that of Sun et al (2017). Sun et al (2017) also included a report that compared treatments with bortezomib and dexamethasone along with studies that included treatments with immunomodulatory agents and dexamethasone (20). While survival outcomes were similar between the two studies, a clear difference was observed for one major adverse outcome: anemia.…”

Section: Discussionmentioning

confidence: 99%

“…Several randomized controlled trials (RCTs) have been conducted to investigate this in relapsed or refractory MM (RRMM), but the results have been controversial (14)(15)(16)(17)(18)(19). performed meta-analyses of triplet versus doublet therapy regimen RCTs for RRMM patients, but none of these studies focused speci cally on dexamethasone with an immunomodulatory drug (20)(21)(22)(23). Therefore, we conducted this meta-analysis to compare the e cacy and safety of triplet combinations that included dexamethasone and an immunomodulatory agent versus the former standard of care doublet combination of dexamethasone and an immunomodulatory drug in patients with RRMM.…”

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confidence: 99%

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Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

Gao

Yan

et al. 2020

Preprint

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Background Triplet therapy has become the standard of care for relapsed or refractory multiple myeloma (RRMM) over the past few years. Prior to that, doublet therapy including dexamethasone and an immunomodulatory were standard. Several systematic studies have been conducted and many combinations with variable triplet therapies but have not always used the former standard therapy as a benchmark. The objective of this meta-analysis was to evaluate the efficacy and safety of triplet combinations that included dexamethasone and an immunomodulatory drug versus a doublet combination of just dexamethasone and an immunomodulatory for the treatment of RRMM. Methods A comprehensive literature search (PubMed, EMBASE, Cochrane Library) for phase III randomized controlled trials for efficacy and safety of triplet versus doublet combinations that specifically included dexamethasone and an immunomodulatory drug for treatment of RRMM. Efficacy (ORR, PFS, OS) and adverse events (≥ grade 3) were assessed using traditional statistical measures for aggregate data. Results Of 235 potential reports, 6 met the inclusion criteria (N = 115–792 participants). The methodological quality was ≥ 4 Jadad score for each. Triplet treatment had higher ORR (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001), PFS (HR = 0.63, 95%CI: 0.52–0.75, P ≤ 0.001), and OS (HR = 0.74, 95%CI: 0.65–0.84, P ≤ 0.001). The incidence of ≥ grade 3 diarrhea and fatigue were significantly higher in the triplet combination group. There was a trend toward increased incidence of ≥ grade 3 neutropenia, thrombocytopenia, thromboembolism, and peripheral neuropathy in the triplet therapy group. Notably, triplet therapy had a significantly lower rate of anemia compared to doublet therapy. Conclusions This study reinforces current guidelines and recommendations for triplet combinations containing dexamethasone and an immunomodulatory drug.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

Gao

Yan

et al. 2020

Preprint

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“…As a rule, in the management of RRMM it is generally accepted that rescue regimens should include drugs with different mechanisms of action to those previously administered, particularly in patients with short PFS duration or suboptimal response [45]. In this field, several clinical trials have confirmed that combination of three drugs are associated to better results in terms of quality and duration of response (DoR) when compared with a two-drug regimen [46]. Therefore, the recommendation is to treat with a triplet chosen according to refractoriness to previous treatments so that the new regimen includes two drugs to which the patient is not refractory.…”

Section: Treatment Of Relapsed Multiple Myelomamentioning

confidence: 99%

Recent Advances in the Treatment of Patients with Multiple Myeloma

Legarda

Cejalvo

Rubia

2020

Cancers

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In the past 20 years, few diseases have seen as great progress in their treatment as multiple myeloma. With the approval of many new drugs and the limited availability of clinical trials comparing head-to-head the different possible combinations, the choice of the best treatments at each stage of the disease becomes complex as well as crucial since multiple myeloma remains incurable. This article presents a general description of the novelties of the whole treatment of multiple myeloma, from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses, including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research, and that will surely play a relevant role in the treatment of this devastating disease in the coming years.

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“…There is no standard of care for MM relapse after autologous HSCT [183,184]. Regimens that are composed of combination therapy with (1) drugs having synergistic effect and no crossresistance and (2) one or two novel therapies are generally preferred as they lead to deeper and longer responses that are translated into improved survival [16,[183][184][185]. However, treatment should be individualized based on toxicity as well as patient and disease characteristics [184].…”

Section: Refractory And/or Relapsed MM (R/r-mm)mentioning

confidence: 99%

“…A meta-analysis of phase III randomized controlled trials showed that, compared to doublet regimens, triplets resulted in improved OS, PFS, very good partial response and CR although the risk of having grade III/IV drug adverse effects was higher with triplet regimens [185].…”

Section: Refractory And/or Relapsed MM (R/r-mm)mentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies

Al-Anazi¹

2019

Update on Multiple Myeloma

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Multiple myeloma is the second commonest hematologic malignancy. It is characterized by neoplastic proliferation of a single clone of plasma cells in the bone marrow producing a monoclonal immunoglobulin and ultimately causing various complications and organ dysfunction. Over the last 10 years, management of multiple myeloma has dramatically changed due to the introduction of several novel therapies that have improved the disease outcome and prognosis, as well as the quality of life of patients with myeloma due to their safety, tolerability and efficacy. Additionally, the widespread utilization of autologous hematopoietic stem cell transplantation, which is still the standard of care for transplant-eligible patients, and the implementation of new therapeutic strategies such as drug combinations in addition to consolidation and maintenance therapies have resulted in further improvements in response rates and survival in patients with multiple myeloma. This book chapter will be an update on the novel therapies and the recent treatment strategies in myeloma. The role of stem cell treatments in the era of novel therapies will be discussed thoroughly.

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Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: A meta-analysis of phase III randomized controlled trials

Cited by 26 publications

References 19 publications

Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

Immunomodulatory drug and dexamethasone-containing triple versus doublet combination treatments for relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials

Recent Advances in the Treatment of Patients with Multiple Myeloma

Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies

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