The role of serum-free light chain ratios in the prediction of poor prognosis in multiple myeloma patients: a systematic review and meta-analysis

Figures & data

Figure 1. Literature screening flow chart.

Table 1. Baseline characteristics of included studies.

Author	Year	Country	Participants	Study design	Kidney function	Number	Recruitment period	Age (years)	Follow up	Outcomes	NOS score
Dejoie	2016	France	Newly diagnosed MM	RCT	Exclusion criteria were the presence serum creatinine >25 mg/L or a creatinine clearance of <60 mL per minute	113	Between November 2010 and December 2012	59 (29–66)	Median follow-up duration was 3.4 years (95% confidence interval: 3.3–3.7 years)	OS and PFS	8
Du	2020	China	Newly diagnosed MM	Retrospective	Serum creatinine ≥ 2 mg/dL was found in 128 (21.5%) patients	595	From June 2010 to December 2016	61 (23–96)	The median estimated follow-up was 48.67 months (95% CI: 38.31–59.03 months)	OS and PFS	8
Giarin	2009	Italy	Newly diagnosed MM after stem cell transplantation	Unknown	Unclear	203	From July 1995 to February 2006	56 (33–74)	37 (10–117) months	OS and EFS	7
Kumar	2010	America	Newly diagnosed MM	RCT	Unclear	314	From February 1988 to May 1992	Not mentioned	Maximal follow-up was 14 years	OS and PFS	8
Moustafa	2015	America	Newly diagnosed MM	Retrospective	Unclear	449	Between January 2004 and December 2011	65 (29–91)	The estimated median follow-up was 5.5 years (95% confidence interval (CI): 5.0, 5.9)	OS and PFS	8
Özkurt	2017	Turkey	MM patients undergoing autologous stem cell transplantation	Retrospective	Unclear	70	Between September 2003 and January 2010	54 (28–68)	Median follow-up was 15.3 (6.0–68.0) months	OS and PFS	8
Silva	2016	Spain	Newly diagnosed MM	Retrospective	Serum creatinine ≥ 2 mg/dL was found in 32 (18%) patients	180	From May 2008 to May 2015	69 (61 ± 76)	A median time of 35 (18 ± 61) months	OS and PFS	8
Snozek	2008	America	Newly diagnosed MM	Prospective	Creatinine: 1.2 (0.5–18.2) (mg/dl)	790	From January 1, 1985 through December 31, 1998	66 (20–92)	The median duration of follow-up is 8.4 years	OS	7
Tacchetti	2016	Italy	Newly diagnosed MM	Retrospective	Creatinine: 1.0 (0.8–1.34) (mg/dl)	150	Between July 2006 and July 2013	63 (57–71)	3 years	OS and PFS	8

sFLC = serum free light chain; RCT = randomized controlled trial; MM = multiple myeloma; OS = overall survival; PFS = progression-free survival.

Table 2. Abnormal sFLC ratio in the included studies.

Author	Abnormal sFLC ratio
Dejoie	Reference ranges for κ sFLC were 3.3 to 19.4 mg/L; for λ sFLC, 5.7 to 26.3 mg/L; and for the κ:λ sFLC ratio, 0.26–1.65.
Du	FLC assay measures absolute free κ and λ light chain values and by default is reported as the κ/λ ratio (normal range, 0.26–1.65)
Giarin	free κ 3.3–19.4 mg/L, free λ 5.7–26.3 mg/L, and sFLC κ/λ ratio 0.26–1.65.
Kumar	In addition to reporting the κ- and λ-FLC, the assay report also contains the κ/λ FLC ratio (diagnostic range: 0.26–1.65).
Moustafa	The following ranges as our reference for normal FLC values; κ FLC (0.33–1.94 mg/dl), λ FLC (0.57–2.63 mg/dl), and (0.26–1.65) for the sFLC κ/λ ratio.
Özkurt	Normal ranges were 3.3–19.4 mg⁄ L for kappa (κ) and 5.7–26.3 mg⁄ L for lambda (λ) FLC. FLC ratio was calculated as κ⁄λ. A normal FLC ratio [κ⁄λ] range was defined as 0.26–1.65. FLC ratio >1.65 indicated excess κFLC and FLC ratio <0.26 excess λFLC, respectively.
Silva	≥47
Snozek	It allows the assessment of clonality based on the FLC ratio, which is calculated as κ/λ, that is, free κ concentration divided by free λ (reference interval, 0.26–1.65)
Tacchetti	≥100

sFLC = serum free light chain; RCT = randomized controlled trial; MM = multiple myeloma; OS = overall survival; PFS = progression-free survival.

Figure 2. Forest plot of the association between sFLC ratio and OS.

Figure 3. Funnel plot of the association between sFLC ratio and OS.

Figure 4. Sensitivity analysis of the association between sFLC ratio and OS.

Figure 5. Galbraith plot of the association between sFLC ratio and OS.

Figure 6. Forest plot of the association between sFLC ratio and PFS.

Figure 7. Funnel plot of the association between sFLC ratio and PFS.

Figure 8. Sensitivity analysis of the association between sFLC ratio and PFS.

Figure 9. Galbraith plot of the association between sFLC ratio and PFS.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.