- 學位論文
針對初診斷原發性免疫球蛋白輕鏈類澱粉沉積症患者DaraVCD 與其他治療方法的療效比較
Comparison on Efficacy Among DaraVCD and Other Treatments in Patients With Newly Diagnosed Primary Immunoglobulin Light Chain (AL) Amyloidosis with Cardiac Involvement
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摘要
研究背景 原發性免疫球蛋白輕鏈類澱粉沉積症是一種由克隆性漿細胞過度產生異常免疫球蛋白輕鏈所引起的全身性疾病。這是一種罕見疾病，可能會危及生命，尤其是在心臟受影響且進而引發心衰竭時。 原發性免疫球蛋白輕鏈類澱粉沉積症是一種罕見的高死亡率疾病，目前仍沒有有效療法，其治療的發展主要仿自於另一個相關疾病，多發性骨髓瘤。 本研究旨在使用網絡統合分析，將daratumumab + VCD (DaraVCD) 與其他三種曾經用於此種疾病療法的療效做比較，包括melphalan+ dexamethasone (MDex), bortezomib + cyclophosphamide and dexamethasone (VCD); bortezomib + melphalan + dexamethasone (BMDex)。 研究方法 我們進行了系統文獻檢索，從 2010 年 1 月01日至 2022 年 9 月30日的相關文章。使用了以下關鍵字：原發性類澱粉沉積症，新診斷，療法，化療，daratumumab，bortezomib，dexamethasone，心臟反應。系統回顧後納入了七個符合條件的研究，從文獻中收集了血液學反應率和心臟反應率數據並進行了網絡統合分析。 研究結果 根據我們的研究結果顯示，以總體反應率(ORR)而言，DaraVCD 療法最有可能讓患者達到較佳的血液學反應。其次是BMDex（OR：0.48，CI：0.21 - 1.09），VCD (OR: 0.29, CI: 0.16 – 0.54) ，MDex則療效反應最少 (OR: 0.18, CI: 0.07 - 0.45)。 而在心臟療效反應的分析結果與血液學反應一致，DaraVCD可以帶來較佳的心臟療效，其次是 VCD（OR：0.40；CI：0.23-0.71）和 BMDex（OR：0.36；CI：0.14-0.94），MDex 的反應率最低（OR ：0.26；CI：0.08 - 0.82）。 研究結論 根據我們的分析結果，DaraVCD可能對此類患者帶來較佳的血液學反應和心臟反應。然而值得注意的是，BMDex 也顯示與DaraVCD可能有相近的效果，因為這兩者95% 信賴區間重疊。因此，在原發性 AL 澱粉樣變性患者中對 DaraVCD 和 BMDex 進行直接比較非常重要，以確定這種罕見疾病的最佳治療方法。
並列摘要
Background Primary immunoglobulin light chain (AL) amyloidosis is a systemic disease caused by clonal plasma cells which over produce aberrant immunoglobulin light chains. AL amyloidosis is rare but may become life-threatening, especially while heart is involved and with resultant cardiac failure. Though AL amyloidosis with cardiac involvement and failure is highly fatal, its treatment development has been mainly derived from its sister disease- multiple myeloma, which means that there are so far lack of specific treatment nor treatment guideline for AL amyloidosis. Therefore, we aim to use meta-analysis to evaluate the efficacy of daratumumab + bortezomib+cyclophosphamide+dexamethasone (DaraVCD) as the first line treatment and to compare with the other treatments that ever used in AL amyloidosis, e.g., melphalan+ dexamethasone (MDex), VCD; bortezomib + melphalan + dexamethasone (BMDex). Method Systematically literature research had been performed and surveyed relevant articles from 1st January 2010 to 30th September 2022. The following keywords were used: Amyloidosis, AL amyloidosis, newly diagnosed, treatment, chemotherapy, daratumumab, bortezomib, dexamethasone, cardiac, responses. There were seven eligible studies enrolled after the systematical review, and the hematologic response rate and cardiac response rate data were collected and used for network meta-analysis. Result DaraVCD regimen induced better hematologic response, in terms of higher overall response rate (ORR). The comparison on ORR among DaraVCD (as the reference) and the others showed, in order of efficacy, BMDex (OR: 0.48, CI: 0.21 - 1.09) followed by VCD (OR: 0.29, CI: 0.16 – 0.54) and MDex (OR: 0.18, CI: 0.07 - 0.45). Similar to the hematologic response, DaraVCD has the highest cardiac response among all these treatments, followed by VCD (OR: 0.40; CI: 0.23 - 0.71) and BMDex (OR: 0.36; CI: 0.14 - 0.94), MDex had the lowest response rate（OR ：0.26；CI：0.08 - 0.82）. . Conclusion According to our meta-analysis, DaraVCD seems to be the most effective regimen for patients with primary AL amyloidosis. However, BMDex also showed equivocally since their 95% confidence interval overlapped. Therefore, to conduct a head-to-head comparison between DaraVCD and BMDex in patients with primary AL amyloidosis is warranted, to establish the best treatment in such rare disorder.
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