第十二章、支持性療法

• 支持性療法影響患者的生存與生活品質，NCCN 指引強調骨病變與腎功能的管理。

12.1 骨骼病變管理 (Bone Disease)

約85%的MM患者會發展出骨質疏鬆或溶骨性病變 (Osteolytic lesions)，這也是導致患者生活品質下降的主要原因。

• 骨骼修飾藥物選擇與建議：

  • 雙磷酸鹽 (Bisphosphonates，如Zoledronic acid或Pamidronate)。NCCN指引將其列為Category 1建議，適用於所有接受骨髓瘤治療的有症狀患者，無論影像學是否已證實骨病變。⁽¹⁾

  • Denosumab (Xgeva®)。第三期試驗顯示，在預防骨骼相關事件 (Skeletal related events, SREs) 方面，Denosumab 不劣於 Zoledronic acid，且在腎功能下降發生率較低 (10% vs 17%)，而其他副作用如下顎骨壞死或低血鈣則無顯著差異。⁽⁷⁶⁾

• NCCN 指引建議：

  • 腎功能考量：對於嚴重腎功能不全的患者，Denosumab 是首選。若使用雙磷酸鹽，必須密切監測腎功能並依肌酸酐清除率調整劑量。⁽¹⁾

  • 下顎骨壞死 (ONJ) 預防：所有患者在開始使用骨骼修飾藥物前，強烈建議進行全面的牙科檢查。治療期間應定期監測，並在進行侵入性牙科手術前諮詢專科意見。

  • 治療持續時間：建議治療可持續長達2 年。2 年後應由醫師根據患者的疾病狀態與風險進行個別化評估，決定是否繼續或暫停。

12.2 高血鈣症 (Hypercalcemia)

• 急性期處理：包括積極的水分補充 (Hydration)、類固醇、Calcitonin以及雙磷酸鹽 (Zoledronic acid 為首選)。⁽¹⁾

• 長期控制：控制骨髓瘤本身是解決高血鈣的根本方法。

12.3 高黏滯血症 (Hyperviscosity)

• 症狀：常見於 IgM 或 IgA 型骨髓瘤，可能導致頭痛、視力模糊、黏膜出血或神經症狀。

• 處置：對於有症狀的高黏滯血症，血漿置換術 (Plasmapheresis) 是標準的輔助療法，能快速降低血清黏度，緩解症狀。

12.4 貧血 (Anemia)

• 紅血球生成素 (EPO)：可考慮用於有症狀的貧血患者，特別是伴隨腎衰竭者。但在使用前應評估內源性EPO濃度，並注意血栓風險。

12.5 感染預防 (Infection Prevention)

隨著免疫療法 (如雙特異性抗體、CAR-T) 的應用，感染風險顯著增加。⁽¹⁾

• 帶狀皰疹 (Herpes Zoster)：所有接受 Proteasome Inhibitor (PI) (如 Bortezomib) 或 Daratumumab 治療的患者，均應接受抗病毒預防 (如 Acyclovir 或 Valacyclovir)。

• 肺囊蟲肺炎 (PJP)：對於接受高劑量類固醇、特定化療或單株抗體治療的高風險患者，建議進行 PJP 預防。

• 免疫球蛋白補充 (IVIG)：對於反覆發生嚴重感染且伴隨低免疫球蛋白血症 (Hypogammaglobulinemia) 的患者，可考慮定期給予 IVIG。

12.6 血栓預防 (VTE Prophylaxis)

MM 患者本身即為靜脈血栓栓塞 (VTE) 的高風險族群，特別是在使用免疫調節藥物 (IMiDs) (如 Thalidomide, Lenalidomide, Pomalidomide) 時。

• 風險評估模型：NCCN指引建議以 SAVED Score 或 IMPEDE Score 進行風險分層。⁽⁷⁷⁾

• SAVED Score 因子：手術 (Surgery, +2)、亞裔 (Asian, -3)、VTE 病史 (Venous thromboembolism, +3)、年齡 >80 (Eighty, +1)、Dexamethasone 劑量 (高劑量, +2 (每療程> 160 mg) 標準劑量, +1 (每療程120~160 mg))。

  • 低度風險 (SAVED分數 ≤ 3)：6個月VTE風險為3.3%，無須預防。大多數亞裔患者均為此類，栓塞風險相較於西方族群低很多。

  • 中度風險 (SAVED分數 4~7)：6個月VTE風險為8.3%，須考慮VTE預防性療法。

  • 高度風險 (SAVED分數 8)：6個月VTE風險為15.2%，建議預防。

• 預防策略：

  • 低至中度風險：建議使用阿斯匹靈 (Aspirin 81-325 mg)。

  • 高風險：建議使用低分子量肝素 (LMWH) 或全劑量 Warfarin，或直接口服抗凝血劑 (DOACs)。

12.7 腎臟疾病管理 (Renal Disease)

腎功能不全在 MM 患者中極為常見 (約 20-50%) ，主要原因是輕鏈管型腎病變 (Light chain cast nephropathy)。

• 診斷流程：若出現不明原因的腎衰竭或蛋白尿，應進行腎臟切片以區分管型腎病變、類澱粉沉積症 (Amyloidosis) 或單株免疫球蛋白沉積病 (MIDD)。

• 治療策略：

  • 快速降低輕鏈：使用治療起效快的藥物組合，如 Bortezomib + Dexamethasone 或含 Cyclophosphamide 的方案。

  • Daratumumab：研究顯示 Daratumumab 在嚴重腎功能不全甚至透析患者中是安全的，且無需調整劑量，能有效改善腎功能。

  • 高截斷透析 (High-cutoff hemodialysis)：對於急性腎衰竭且輕鏈極高的患者，可考慮使用高截斷透析膜以移除游離輕鏈，但其臨床獲益仍有爭議，需視個案決定。

  • 液體補充：維持足夠的尿量 (每日 >3 公升) 對於預防管型形成至關重要。

12.8 中樞神經系統疾病 (CNS Disease)

CNS 侵犯 (如腦膜骨髓瘤) 是 MM 的罕見但嚴重併發症，預後極差。

• 診斷：腦脊髓液 (CSF) 分析與 MRI 影像。

• 治療：

  • 鞘內療法 (Intrathecal therapy)：包含Methotrexate, Cytarabine, Steroids。

  • 全身性治療：應選擇能穿透血腦屏障 (BBB) 的藥物，如 Pomalidomide, Marizomib (試驗中) 或高劑量 Methotrexate。

  • 放射治療：用於局部病灶控制。

結論

• 第一線療法的典範轉移-四藥組合。無論是適合移植的患者 (Dara-VRd, Isa-VRd) 或是非移植候選者 (Dara-VRd, Isa-VRd, DRd) ，在標準治療中加入抗CD38單株抗體已成為提升治療深度與延長存活的關鍵策略。

• 早期復發 (1-3 線) 的治療標準化：治療選擇高度依賴於患者是否對 Lenalidomide 難治。含抗 CD38 抗體的三藥組合 (如 DKd, Isa-Kd, DPd, DVd) 已成為標準護理。對於適合的患者，以 Carfilzomib 為基礎的方案 (如 KRd) 提供了強效的替代選擇。

• 免疫治療重塑晚期復發 (>3 線) 治療：BCMA 靶向免疫療法 (Cilta-cel, Ide-cel CAR-T 以及 Teclistamab, Elranatamab 等雙特異性抗體) 提供了前所未有的深度緩解率。靶向GPRC5D的新藥Talquetamab，為BCMA治療後復發的患者提供下一線選擇。

• 精準醫療的實踐：Venetoclax 在 t(11;14) 患者中的獨特應用，標誌著骨髓瘤治療向生物標記驅動的精準醫療邁進。

• 支持性照護的優化：Denosumab 在腎功能不全患者中的獨特角色，以及在使用高強度免疫療法時對感染與神經毒性的主動管理。

作者: 傅彥崴藥師

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