Aneeta Channar, Syed Arsalan Ahmed Naqvi, Muhammad Ali Khan, Arifa Bibi, Akshat Saxena, Nikita Tripathi, Ahmad Iftikhar, Ammad Raina, Kaneez Zahra Rubab Khakwani, Irbaz Bin Riaz, Muhammad Husnain
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Recently, the addition of anti-CD38 monoclonal antibodies (mAbs) to the triplet regimen, comprising a proteasome inhibitor, an immunomodulatory agent, and a steroid, for transplant-eligible newly diagnosed multiple myeloma (TENDMM) has shown promising results.</p>\n </section>\n \n <section>\n \n <h3> Aims</h3>\n \n <p>To evaluate the overall efficacy and safety of quadruplet therapy with an anti-CD38 mAb compared to a triplet regimen.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A systematic search of Medline, Scopus, and EMBASE databases from inception to July 2024 identified relevant randomized controlled trials (RCTs). Efficacy and safety outcomes were derived using random-effects meta-analysis. Summarized outcomes include hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratios (OR) for response rates, measurable residual disease (MRD) negativity rate, and grade 3 or higher adverse events (G ≥ 3 AEs).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Five RCTs involving 2963 patients were included. A statistically significant PFS was observed for quadruplet therapy when compared to the triplet regimen (HR 0.44; 95% Confidence Interval [CI] 0.35–0.56). PFS benefit was consistent for the standard risk (SR) group (HR 0.38; 95% CI 0.27–0.52) and high risk (HiR) group (HR 0.62; 95% CI 0.41–0.92). No statistically significant benefit was observed for OS (HR 0.55; 95% CI 0.28–1.08). A statistically significant benefit was observed for the overall response rate (OR 1.77; 95% CI 1.02–3.06) and MRD negativity rate (OR 2.67; 95% CI 1.79–3.99). No significant differences were observed for G ≥ 3 AE (OR 1.21; 95% CI 0.92–1.58), lymphopenia (OR 1.09; 95% CI 0.62–1.89), and anemia (OR 1.06; 95% CI 0.83–1.37). However, a significantly increased risk was observed for all-grade thrombocytopenia (OR 1.64; 95% CI 1.37–1.97), neutropenia (OR 2.24; 95% CI 1.67–3.02) and infections (OR 1.88; 95% CI 1.07–3.31).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Quadruplet therapy demonstrated a favorable efficacy and safety profile, with consistent benefit across subgroups. The findings support its potential as the new standard of care for TENDMM.</p>\n </section>\n </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 4","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70171","citationCount":"0","resultStr":"{\"title\":\"Efficacy and Safety of Quadruplet Therapy in Newly Diagnosed Transplant-Eligible Multiple Myeloma: A Systematic Review and Meta-Analysis\",\"authors\":\"Aneeta Channar, Syed Arsalan Ahmed Naqvi, Muhammad Ali Khan, Arifa Bibi, Akshat Saxena, Nikita Tripathi, Ahmad Iftikhar, Ammad Raina, Kaneez Zahra Rubab Khakwani, Irbaz Bin Riaz, Muhammad Husnain\",\"doi\":\"10.1002/cnr2.70171\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The treatment landscape for multiple myeloma continues to evolve. 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引用次数: 0
摘要
背景 多发性骨髓瘤的治疗形势不断变化。最近，在治疗符合移植条件的新诊断多发性骨髓瘤（TENDMM）的三联疗法（包括蛋白酶体抑制剂、免疫调节剂和类固醇）中加入抗CD38单克隆抗体（mAbs）显示出了良好的效果。 目的 评估抗CD38 mAb四联疗法与三联疗法相比的总体疗效和安全性。 方法 对 Medline、Scopus 和 EMBASE 数据库从开始到 2024 年 7 月的数据进行系统检索，确定了相关的随机对照试验 (RCT)。采用随机效应荟萃分析法得出疗效和安全性结果。总结的结果包括无进展生存期（PFS）和总生存期（OS）的危险比（HR）、反应率的几率比（OR）、可测量残留疾病（MRD）阴性率以及 3 级或以上不良事件（G ≥ 3 AEs）。 结果 共纳入五项研究，涉及 2963 名患者。与三联疗法相比，四联疗法的 PFS 有统计学意义（HR 0.44；95% 置信区间 [CI] 0.35-0.56）。标准风险（SR）组（HR 0.38；95% CI 0.27-0.52）和高风险（HiR）组（HR 0.62；95% CI 0.41-0.92）的PFS获益一致。在 OS（HR 0.55；95% CI 0.28-1.08）方面未观察到有统计学意义的获益。在总体反应率（OR 1.77；95% CI 1.02-3.06）和 MRD 阴性率（OR 2.67；95% CI 1.79-3.99）方面观察到了具有统计学意义的获益。在 G≥3 AE（OR 1.21；95% CI 0.92-1.58）、淋巴细胞减少（OR 1.09；95% CI 0.62-1.89）和贫血（OR 1.06；95% CI 0.83-1.37）方面未观察到明显差异。然而，观察到全血细胞减少症（OR 1.64；95% CI 1.37-1.97）、中性粒细胞减少症（OR 2.24；95% CI 1.67-3.02）和感染（OR 1.88；95% CI 1.07-3.31）的风险明显增加。 结论 四联疗法具有良好的疗效和安全性，各亚组患者均可从中获益。研究结果支持四联疗法成为治疗TENDMM的新标准。
Efficacy and Safety of Quadruplet Therapy in Newly Diagnosed Transplant-Eligible Multiple Myeloma: A Systematic Review and Meta-Analysis
Background
The treatment landscape for multiple myeloma continues to evolve. Recently, the addition of anti-CD38 monoclonal antibodies (mAbs) to the triplet regimen, comprising a proteasome inhibitor, an immunomodulatory agent, and a steroid, for transplant-eligible newly diagnosed multiple myeloma (TENDMM) has shown promising results.
Aims
To evaluate the overall efficacy and safety of quadruplet therapy with an anti-CD38 mAb compared to a triplet regimen.
Methods
A systematic search of Medline, Scopus, and EMBASE databases from inception to July 2024 identified relevant randomized controlled trials (RCTs). Efficacy and safety outcomes were derived using random-effects meta-analysis. Summarized outcomes include hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratios (OR) for response rates, measurable residual disease (MRD) negativity rate, and grade 3 or higher adverse events (G ≥ 3 AEs).
Results
Five RCTs involving 2963 patients were included. A statistically significant PFS was observed for quadruplet therapy when compared to the triplet regimen (HR 0.44; 95% Confidence Interval [CI] 0.35–0.56). PFS benefit was consistent for the standard risk (SR) group (HR 0.38; 95% CI 0.27–0.52) and high risk (HiR) group (HR 0.62; 95% CI 0.41–0.92). No statistically significant benefit was observed for OS (HR 0.55; 95% CI 0.28–1.08). A statistically significant benefit was observed for the overall response rate (OR 1.77; 95% CI 1.02–3.06) and MRD negativity rate (OR 2.67; 95% CI 1.79–3.99). No significant differences were observed for G ≥ 3 AE (OR 1.21; 95% CI 0.92–1.58), lymphopenia (OR 1.09; 95% CI 0.62–1.89), and anemia (OR 1.06; 95% CI 0.83–1.37). However, a significantly increased risk was observed for all-grade thrombocytopenia (OR 1.64; 95% CI 1.37–1.97), neutropenia (OR 2.24; 95% CI 1.67–3.02) and infections (OR 1.88; 95% CI 1.07–3.31).
Conclusion
Quadruplet therapy demonstrated a favorable efficacy and safety profile, with consistent benefit across subgroups. The findings support its potential as the new standard of care for TENDMM.
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