Q1. Which criteria is not myeloma-defining event?¶

(A) One or more osteolytic bone lesions on skeletal radiography, CT, or FDG PET/CT.
(B) Involved:uninvolved serum FLC ratio ≥10 and involved FLC concentration 10 mg/dL or higher.
(C) Renal insufficiency (creatinine >2 mg/dL).
(D) Clonal bone marrow plasma cells ≥60%.

點此顯示正解

(B) Involved:uninvolved serum FLC ratio ≥10 and involved FLC concentration 10 mg/dL or higher.

詳解¶

Option (B) is NOT a myeloma-defining event because it uses incorrect thresholds for the serum free light chain (FLC) criteria. The correct IMWG 2014 criteria require an involved:uninvolved FLC ratio ≥100 (not ≥10) AND an involved FLC concentration ≥100 mg/L (not 10 mg/dL).²[^6][8]

Why Option (B) Fails to Meet Myeloma-Defining Event Criteria¶

The IMWG 2014 updated criteria established specific biomarkers (the "SLiM" criteria) that define active multiple myeloma requiring treatment, even in the absence of CRAB features. For the serum FLC ratio criterion, both conditions must be met²[^8]: - Involved:uninvolved serum FLC ratio ≥100 - Involved FLC level ≥100 mg/L

Option (B) states a ratio of ≥10 and involved FLC of 10 mg/dL (100 mg/L), which falls far short of the ratio threshold. While a ratio of ≥10 may indicate increased progression risk in smoldering myeloma, it does not meet the threshold for active myeloma diagnosis. The IMWG selected the ratio of ≥100 based on studies showing approximately 72-79% risk of progression to active myeloma within 2 years at this threshold.[^8][9]

Why the Other Options ARE Myeloma-Defining Events¶

(A) One or more osteolytic bone lesions on skeletal radiography, CT, or FDG PET/CT is a classic CRAB criterion (the "B" for bone lesions) and represents end-organ damage attributable to the plasma cell disorder.¹²

(C) Renal insufficiency with creatinine >2 mg/dL is the "R" in CRAB criteria. The IMWG 2014 criteria define renal insufficiency as creatinine clearance <40 mL/min or serum creatinine >177 μmol/L (>2 mg/dL).²

(D) Clonal bone marrow plasma cells ≥60% is one of the three specific biomarkers added in the 2014 IMWG update (the "S" in SLiM). This threshold is associated with approximately 80% risk of progression to symptomatic end-organ damage and qualifies as a myeloma-defining event even without CRAB features.¹²[^6]

The 2014 IMWG criteria represented a paradigm shift, allowing diagnosis and treatment initiation before irreversible end-organ damage occurs in patients with these high-risk biomarkers.¹[^6]

詳解 · 中文翻譯¶

選項 (B) 不是骨髓瘤定義事件，因為它使用血清遊離輕鏈（FLC）標準的不正確閾值。正確的 IMWG 2014 標準需要 關聯：無關聯血清 FLC 比 ≥100（不是 ≥10）及一個 關聯 FLC 濃度 ≥100 mg/L（不是 10 mg/dL）²[^6][8]。

為何選項 (B) 未達骨髓瘤定義事件標準¶

IMWG 2014 更新標準建立特定生物標誌物（「SLiM」標準），定義活躍多發性骨髓瘤需要治療，即使在缺乏 CRAB 特徵的情況下。對於血清 FLC 比標準，兩個條件必須相遇²[^8]： - 關聯：無關聯血清 FLC 比 ≥100 - 關聯 FLC 水準 ≥100 mg/L

選項 (B) 陳述比 ≥10 及關聯 FLC 10 mg/dL（100 mg/L），遠低於比閾值。雖然比 ≥10 可能表示粉紅色骨髓瘤中進展風險增加，它不滿足活躍骨髓瘤診斷的閾值。IMWG 基於研究顯示在此閾值有約 72-79% 的 2 年內進展風險選擇了 ≥100 比[^8][9]。

為何其他選項是骨髓瘤定義事件¶

(A) 一個或更多溶骨性骨病變在骨骼放射攝影、CT 或 FDG PET/CT 上是經典 CRAB 標準（「B」代表骨病變）及代表可歸因於漿細胞病症的器官末期損害¹²。

(C) 腎功能不全伴肌酸酐 >2 mg/dL 是 CRAB 標準中的「R」。IMWG 2014 標準定義腎功能不全為肌酸酐清除率 <40 mL/min 或血清肌酸酐 >177 μmol/L（>2 mg/dL）²。

(D) 隆骨髓漿細胞 ≥60% 是 2014 IMWG 更新加入的三個特定生物標誌物之一（SLiM 中的「S」）。此閾值與約 80% 進展至症狀性器官末期損害風險相關聯，且即使無 CRAB 特徵也符合骨髓瘤定義事件¹²[^6]。

2014 IMWG 標準代表典範轉移，允許在具有這些高風險生物標誌物的患者中在不可逆器官末期損害發生之前進行診斷及治療開始¹[^6]。

參考文獻 (AMA)¶

Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group Updated Criteria for the Diagnosis of Multiple Myeloma. The Lancet. Oncology. 2014;15(12):e538-48. doi:10.1016/S1470-2045(14)70442-5. PMID:25439696. ↩↩↩↩↩↩
Rajkumar SV. Multiple Myeloma: 2022 Update on Diagnosis, Risk Stratification, and Management. American Journal of Hematology. 2022;97(8):1086-1107. doi:10.1002/ajh.26590. PMID:35560063. ↩↩↩↩↩↩↩↩↩↩
Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and Management of Multiple Myeloma: A Review. Jama. 2022;327(5):464-477. doi:10.1001/jama.2022.0003. PMID:35103762. ↩

Slide annotations

Clonal BM plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma. Myeloma-defining events (MDE). CRAB criteria: Calcium (hyperCa, >2.75 mmol/L; >11 mg/dL), Renal impairment (> 2 mg/dL; CCr < 40 ml/min), Anemia (< 10 g/dL; >2 g/dL below the LLN), Bony disability (≥1 on X-ray, CT/PET-CT). SLiM criteria: S (clonal bone marrow plasmacytosis ≥60%), Li (I/U serum FLC ≥100; involved FLC ≥100 mg/L), M (> 1 focal lesions on MRI, at least 5 mm in size).