Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma

Iida, Shinsuke; Wakabayashi, Masashi; Tsukasaki, Kunihiro; Miyamoto, Ken‐ichi; Maruyama, Dai; Yamamoto, Kazuhito; Takatsuka, Yuichi; Kusumoto, Shigeru; Kuroda, Junya; Ando, Kiyoshi; Kikukawa, Yoshitaka; Yasukawa, Masaki; Kobayashi, Miki; Hanamura, Ichiro; Asai, Hiroaki; Nagai, Hirokazu; Shimada, Kazuyuki; Tsukamoto, Norifumi; Inoue, Yoshiko; Tobinai, Kensei

doi:10.1111/cas.13550

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…The main limitation of this study is that the efficacy outcomes for both the aponermin group and the placebo groups were slightly weaker compared with the triplet regimens of novel drugs approved in recent years. In particular, the ORR of the placebo group was only 13.7%, which was lower than previously reported [ 26 – 28 ]. However, cross-trial comparisons are confounded by differences in patients populations and study designs.…”

Section: Discussioncontrasting

confidence: 84%

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Xia,

Leng,

Fang

et al. 2023

BMC Cancer

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Background Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. Methods Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). Results A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49–0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. Conclusions Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. Trial registration The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

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Section: Discussioncontrasting

confidence: 84%

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Xia,

Leng,

Fang

et al. 2023

BMC Cancer

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“…Thus, a total of 37 citations were included for full‐text analysis. These citations included 37 RCTs comprising 37 full publications 12–48 . In addition, 30 Phase III RCTs and seven Phase II RCTs were identified on http://clinicaltrials.gov.…”

Section: Resultsmentioning

confidence: 99%

“…The pooled HR was used in the full NMA (HR, 0.82; 95% CI, 0.68–0.99). Tables 1 and S1 list the summary characteristics of all 34 treatment options and 37 RCTs 12–48 . Across all RCTs, a total of 14 293 patients with RRMM were included in the analysis.…”

Section: Resultsmentioning

confidence: 99%

Relapsed and refractory multiple myeloma: A systematic review and network meta‐analysis of the efficacy of novel therapies

et al. 2023

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I N TRODUC TIONAdvances in the use of bortezomib as a proteasome inhibitor (PI) and lenalidomide as an immunomodulatory drug (IMID) in early-stage multiple myeloma (MM) therapy have improved both the progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed MM. 1,2 However, all patients eventually relapse and require further treatments. Thus, relapsed/refractory MM (RRMM) is the main challenge of recent clinical research. Specifically, pomalidomide as an IMID, ixazomib or carfilzomib as second-generation PIs, and anti-CD38 (daratumumab and isatuximab) or anti-SLAMF-7 (elotuzumab) monoclonal antibodies are being used in addition to the above drugs, and many combinations of two or three of these agents have been investigated for the treatment of RRMM. Under such circumstances, understanding which regimens are better than others is not easy. The evolving field of treatment options, such as the recently approved agents selinexor (a first-in-class selective inhibitor of nuclear export), melflufen (a peptide-drug conjugate), and venetoclax (a BCL2 inhibitor),

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“…The median OS was not attained, the mean PFS was 35.1 months (95% CI, 30.9-not reached), and the mean follow-up period was 30 months. Additionally, a phase 2 study (JCOG0904) ( 48 ) revealed that patients with RRMM undergoing VRD treatment exhibited satisfactory 1-year PFS (45.5%) and 3-year OS (70%) outcomes.…”

Section: Clinical Research and Applicationmentioning

confidence: 99%

Lenalidomide use in multiple myeloma (Review)

Zhang,

Wang,

2023

Mol Clin Oncol

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Lenalidomide is a second-generation new immunomodulatory medication used to treat multiple myeloma (MM). Its mechanism of action involves affecting the expression of vascular endothelial growth factor, interleukin-6, cytochrome c , caspase-8, as well as other factors including immunological modulation and the direct killing of cells, among others, rendering it a fundamental medication, useful for the treatment of MM. Combining lenalidomide with other medications such dexamethasone, bortezomib, ixazomib, carfilzomib and daratumumab can markedly alleviate MM. When autologous-hematopoietic stem cell transplantation (ASCT) cannot be utilized to treat newly diagnosed individuals with MM (NDMM), monotherapy maintenance following lenalidomide and dexamethasone may be employed. Following ASCT, single-agent maintenance with lenalidomide can be performed as an additional treatment. The combination of bortezomib and lenalidomide has been demonstrated to be associated with favorable response rates, tolerable toxicity, and therapeutic benefits although caution is warranted to prevent the onset of peripheral neuropathy with its use. A new-generation oral drug with an excellent safety profile, ixazomib, is more practical and therapeutically applicable in relapsed refractory MM. However, the frequent occurrence of cardiovascular events, hematocrit, and infections with it require flexible adjustment in its clinical application. Carfilzomib produces a rapid and profound response in patients with NDMM eligible for transplantation, but its cardiovascular side effects need to be closely monitored. The primary aim of the present review was to examine the pharmacological properties and pharmacokinetics of lenalidomide, as well as the efficacy and safety of lenalidomide-based treatments with reference to data from clinical trials and real-world studies.

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Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma

Cited by 8 publications

References 39 publications

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Relapsed and refractory multiple myeloma: A systematic review and network meta‐analysis of the efficacy of novel therapies

Lenalidomide use in multiple myeloma (Review)

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