Involved free light chain: an early independent predictor of response and progression in multiple myeloma

Figures & data

Table 1. Patient characteristics.

	No. of patients (%)
Gender, male no. (%)	262 (58)
Age, years median (IQR)	68 (61–75)
	Median (IQR)
Hemoglobin, g/L	111 (98–124)
Creatinine, μmol/L	87 (67–122)
eGFR, mL/min/1,73 m²	65 (43–78)
Calcium, mmol/L	2.3 (2.2–2.4)
β-2-microglobulin,	3.56 (251–3.56)
Albumin	32 (29–36)
Serum M-spike g/dL	1.8 (0.2–3.5)
Urine M-spike, mg/L	29 (4–321)
Involved FLC, mg/L	149 (36–686)
	No. patients (%)
Abnormal FLC ratio	426 (95)
Heavy chain
IgG	273 (60.9)
IgA	89 (19.9)
IgM and other	6 (1.3)
Light chain only	78 (17.4)
Light chain
Kappa	273 (60.9)
Lambda	175 (39.1)
Cytogenetics
High risk	120 (57.4)
t(4;14)	11 (5.2)
t(14;16)	4 (1.9)
t(14;20)	0 (0)
Gain(1q)	65 (31.1)
Del (17p)	22 (10.5)
Non-hyperdiploidy	65 (31.1)
Standard risk	89 (42.6)
ISS
I + II	240 (57.4)
III	104 (42.6)

Median and interquartile ranges or number and percentages for the different parameters are presented. High risk cytogenetic defined as presence of t(4;14), t(14;16), t(14;49), gain1q, del17/17p, and/or nonhyperdiploidy.

IQR: interquartile range; eGRF: estimated glomerular filtration rate; FLC: free light chain; ISS: International Staging System.

Figure 1. Kaplan–Meier plots of the time to response in first line of treatment measured by involved free light chain (iFLC), serum protein electrophoresis (sPEP) and urine electrophoresis (uPEP). (A) Patients with IgG subtype. (B) Patients with IgA subtype.

Table 2. Time to response (TTR), in months, in the 1st, 2nd, 3rd line of treatment and on all occasions of responses (in all 3 lines).

	n	Median	IQR	p-value
TTR first line
iFLC	450	2.2	1.2–6.9
sPEP	450	5.6	1.7–17.7	<0.001
uPEP	390	19.2	3.7–43.9	<0.001
TTR second line
iFLC	129	1.1	0.5–3.3
sPEP	129	5.4	0.7–12.9	<0.001
uPEP	78	4.7	0.9–11.7	0.002
TTR third line
iFLC	30	0.9	0.6–1.4
sPEP	30	4.8	1.6–18.3	<0.001
uPEP	15	1.3	0.8–7.6	0.13
TTR regardless of line
iFLC	609	1.9	0.1–6.2
sPEP	609	5.4	1.6–16.5	<0.001
uPEP	483	13.3	2.9–39.7	<0.001

The median and interquartile ranges (IQR) are presented for the time to response (TTR) in the first, second, third and on all occasions of responses (in all three lines).

iFLC: involved free light chain; sPEP: serum protein electrophoresis; uPEP: urine protein electrophoresis.

Figure 2. Time to first response measured by involved free light chain (iFLC), serum protein electrophoresis (sPEP) and urine electrophoresis (uPEP). (A) Measurable disease by sPEP only, i.e. >1 g/dl M-protein in serum and iFLC ≤ 10 mg/dl. (B) Measurable disease by sPEP and iFLC, i.e. >1 g/dl M-protein in serum and iFLC > 10 mg/dl. (C) Measurable disease by iFLC and uPEP only, ≤1 g/dl M-protein in serum and >200 mg/24 h M-protein in urine, and iFLC > 10 mg/dl).

Table 3. Time to response, in months, in the first line of treatment grouped by measurable disease.

	n	Median	95% CI	p-value
sPEP and iFLC
iFLC	181	1.8	1.4–2.2
sPEP	182	2.2	1.9–2.7	0.04
uPEP	69	3.9	1.7–6.1	<0.001
sPEP only
iFLC	79	2.2	1.7–2.7
sPEP	80	2.3	1.9–2.9	0.46
uPEP	21	NR	NR	0.002
uPEP and iFLC
iFLC	97	1.4	1.2–1.6
sPEP	49	NR	NR	<0.001
uPEP	87	1.9	1.5–2.3	0.003

sPEP and FLC was defined as >1 g/dL M-protein in serum and iFLC > 10 mg/dL, sPEP only as >1 g/dL M-protein in serum and iFLC ≤ 10 mg/dL, uPEP and iFLC as ≤1 g/dL M-protein in serum and > 200 mg/24 h M-protein in urine and iFLC > 10 mg/dL).

iFLC: involved free light chain; sPEP: serum protein electrophoresis; uPEP: urine protein electrophoresis; NR: not reached.

Table 4. Time to progression (TTP), in months, in the first, second, thirdof treatment and on all occasions of responses (in all three lines).

	n	Median	IQR	p-value
TTP first line
iFLC	302	18.9	8.2–35.1
sPEP	302	18.9	7.5–24.6	0.27
uPEP	182	31.4	15.0–47.6	<0.001
TTP second line
iFLC	53	9.9	1.5–21.9
sPEP	53	11.3	1.9–24.5	0.13
uPEP	34	21.2	9.2–32.6	0.02
TTP third line
iFLC	15	3.6	1.1–16.0
sPEP	15	1.8	0.9–15.8	0.95
uPEP	8	19.4	8.8–40.7	0.122
TTP regardless of line
iFLC	370	16.6	5.8–33.0
sPEP	370	16.7	5.3–34.8	0.098
uPEP	224	29.8	14.1–45.5	<0.001

The median and interquartile ranges are presented median and 95% confidence interval (CI) for the time to progression (TTP) in the first, second, third, and on all occasions of progression (in all three lines).

iFLC: involved free light chain; sPEP: serum protein electrophoresis; uPEP: urine protein electrophoresis.

Figure 3. Time to first progression measured by involved free light chain (iFLC), serum protein electrophoresis (sPEP) and urine electrophoresis (uPEP). (A) Measurable disease by sPEP and iFLC, i.e. >1 g/dl M-protein in serum and iFLC > 10 mg/dl. (B) Measurable disease by sPEP only, i.e. >1 g/dl M-protein in serum and iFLC ≤ 10 mg/dl. (C) Measurable disease by iFLC and uPEP only, ≤1 g/dl M-protein in serum and >200 mg/24 h M-protein in urine, and iFLC > 10 mg/dl).

Table 5. Time to first-line progression, in months, grouped by measurable disease.

	n	Median	95% CI	p-value
sPEP and iFLC
iFLC	152	21.8	15.3–28.45
sPEP	155	21.5	7.5–24.6	0.93
uPEP	130	NR	NR	<0.001
sPEP only
iFLC	74	24.8	3.3–46.3
sPEP	78	51.1		0.003
uPEP	70	NR	NR	<0.001
uPEP and iFLC
iFLC	87	19.6	6.0–33.2
sPEP	87	NR	NR	<0.001
uPEP	86	63.7	–	0.04

sPEP and FLC was defined as >1 g/dL M-protein in serum and iFLC > 10 mg/dL, sPEP only as >1 g/dL M-protein in serum and iFLC ≤ 10 mg/dL, uPEP and iFLC as ≤1 g/dL M-protein in serum and > 200 mg/24 h M-protein in urine and iFLC > 10 mg/dL).

iFLC: involved free light chain; sPEP: serum protein electrophoresis; uPEP: urine protein electrophoresis; NR: not reached.