PHF19 before and post induction treatment possess favorable potency of reflecting treatment response to protease inhibitors, event-free survival, and overall survival in multiple myeloma patients

Figures & data

Table 1. Clinical characteristics of MM patients.

Characteristics	MM patients (N = 69)
Age (years)	65.8 ± 9.0
Age ≥65 years	38 (55.1)
Gender
Male	42 (60.9)
Female	27 (39.1)
Immunoglobulin subtype
IgG	33 (47.8)
IgA	17 (24.6)
Others	19 (27.5)
Bone lesion	50 (72.5)
Renal impairment	33 (47.8)
Hb (g/L)	88.0 ± 21.7
Hb <100 g/L	49 (71.0)
Ca (mg/dL)	11.5 (10.6∼13.2)
Ca <12 mg/dL	29 (42.0)
ALB (g/L)	32.0 (26.6∼38.0)
ALB <35 g/L	44 (63.8)
β2-MG (mg/L)	4.9 (3.3∼9.1)
β2-MG ≥5.5 mg/L	31 (44.9)
LDH (U/L)	212.8 (165.4∼250.8)
LDH ≥220 U/L	28 (40.6)
t (4; 14)	11 (15.9)
t (14; 16)	4 (5.8)
Del (17p)	6 (8.7)
ISS stage
Stage I	11 (15.9)
Stage II	27 (39.1)
Stage III	31 (44.9)
R-ISS stage
Stage I	9 (13.0)
Stage II	37 (53.6)
Stage III	23 (33.3)
Regimens
Bortezomib + lenalidomide + dexamethasone	37 (53.6)
Bortezomib + cyclophosphamide + dexamethasone	20 (29.0)
Bortezomib + dexamethasone	12 (17.4)

The normal distribution was tested using the Kolmogorov-Smirnov test. Data were presented with mean ± SD, numbers (percentage), and median (1st quantile value∼3rd quantile value) properly.

Renal impairment was defined as serum creatinine ≥2 mg/dL.

MM, multiple myeloma; SD, standard deviation; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; IQR, interquartile range; Ca, calcium; ALB, albumin; β₂-MG, beta-2-microglobulin; LDH, lactate dehydrogenase; ISS, international staging system; R-ISS, revised international staging system.

Figure 1. PHF19 expression was aberrantly high and declined post induction treatment in MM patients.

Table 2. Correlation of PHF19 expression with clinical characteristics of MM patients.

Characteristics	PHF19 expression at baseline	P value	PHF19 expression post induction treatment	P value
Age		0.280		0.385
<65 years	2.93 (2.10∼4.41)		2.15 (1.29∼3.34)
≥65 years	3.76 (2.08∼6.24)		2.39 (1.51∼4.05)
Gender		0.091		0.163
Male	3.05 (2.09∼4.28)		2.03 (1.37∼3.34)
Female	4.61 (2.09∼6.87)		2.66 (1.84∼3.88)
Immunoglobulin subtype		0.228		0.530
IgG	2.69 (1.90∼4.99)		2.08 (1.41∼3.39)
IgA	3.92 (2.55∼5.91)		2.33 (1.83∼3.84)
Others	3.85 (2.18∼7.04)		2.33 (1.29∼4.52)
Bone lesion		0.158		0.051
No	3.36 (1.74∼4.20)		1.80 (1.07∼3.00)
Yes	3.36 (2.20∼6.24)		2.39 (1.67∼3.75)
Renal impairment		0.012		0.020
No	3.16 (1.75∼4.36)		1.82 (1.08∼3.26)
Yes	4.26 (2.43∼6.67)		2.83 (1.95∼3.79)
Hb		0.190		0.070
≥100 g/L	3.02 (1.79∼4.74)		1.74 (1.08∼3.34)
<100 g/L	3.57 (2.29∼6.06)		2.32 (1.81∼3.96)
Ca		0.937		0.213
≥12 mg/dL	3.52 (2.09∼5.58)		1.95 (1.26∼3.41)
<12 mg/dL	2.86 (2.11∼5.65)		2.32 (1.90∼3.79)
ALB		0.212		0.077
≥35 g/L	3.21 (1.82∼4.88)		1.92 (1.07∼3.34)
<35 g/L	3.41 (2.33∼5.92)		2.33 (1.80∼3.99)
β2-MG		0.008		0.029
<5.5 mg/L	2.87 (1.87∼4.35)		1.88 (1.24∼3.34)
≥5.5 mg/L	4.26 (2.39∼6.87)		2.83 (1.92∼4.85)
LDH		0.350		0.217
<220 U/L	3.36 (2.07∼4.99)		2.22 (1.27∼3.50)
≥220 U/L	3.30 (2.23∼6.66)		2.29 (1.85∼3.93)
t (4; 14)		0.028		0.019
No	3.16 (2.03∼4.90)		2.18 (1.37∼3.34)
Yes	6.38 (2.86∼8.42)		3.73 (1.88∼5.69)
t (14; 16)		0.719		0.949
No	3.36 (2.07∼5.55)		2.22 (1.46∼3.68)
Yes	3.00 (2.38∼8.42)		2.25 (2.00∼2.80)
Del (17p)		0.609		0.349
No	3.36 (2.18∼5.41)		2.23 (1.60∼3.65)
Yes	2.93 (1.19∼7.32)		1.74 (0.91∼3.61)
ISS stage		0.003		0.004
I	2.10 (1.00∼4.33)		1.40 (0.86∼1.98)
II	3.36 (1.93∼4.48)		2.33 (1.60∼3.65)
III	4.26 (2.39∼6.87)		2.83 (1.92∼4.85)
R-ISS stage		0.002		0.001
I	2.10 (0.97∼3.77)		1.25 (0.81∼1.95)
II	3.36 (2.01∼4.99)		2.33 (1.51∼3.72)
III	4.26 (2.69∼8.15)		2.83 (2.14∼4.85)

Data of PHF19 expression were described as median (1st quantile value∼3rd quantile value).

PHF19, PHD finger protein 19; MM, multiple myeloma; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; Ca, calcium; ALB, albumin; β₂-MG, beta-2-microglobulin; LDH, lactate dehydrogenase; ISS, international staging system; R-ISS, revised international staging system.

Figure 2. PHF19 expression at baseline and post induction treatment were negatively linked with CR and ORR in MM patients. Correlation of PHF19 expression at baseline, post induction treatment, and its change with treatment regimens (A), CR (B), and ORR (C). PHF19 expression change equaled to PHF19 expression post induction treatment minus its expression at baseline.

Figure 3. Abnormal PHF19 expression at baseline and post induction treatment were associated with shorter EFS in MM patients. The accumulating EFS rates (A). Linkage of abnormal PHF19 expression at baseline (B) and post induction treatment (C) with EFS.

Figure 4. Abnormal PHF19 expression at baseline and post induction treatment were associated with shorter OS in MM patients. The accumulating OS rates (A). Linkage of abnormal PHF19 expression at baseline (B) and post induction treatment (C) with OS.

Table 3. Cox regression model of EFS.

Items	HR (95% CI)	P value
Univariable Cox regression model
PHF19 expression at baseline (abnormal vs. normal)	2.424 (1.129∼5.204)	0.023
PHF19 expression post induction treatment (abnormal vs. normal)	2.511 (1.220∼5.167)	0.012
Age (≥65 years vs. < 65 years)	2.036 (0.962∼4.309)	0.063
Gender (female vs. male)	1.564 (0.762∼3.208)	0.223
Immunoglobulin subtype
Others (reference)
(IgG vs. reference)	1.637 (0.670∼3.998)	0.279
(IgA vs. reference)	2.107 (0.720∼6.168)	0.174
Bone lesion (yes vs. no)	1.858 (0.755∼4.572)	0.177
Renal impairment (yes vs. no)	2.249 (1.076∼4.701)	0.031
Hb (<100 g/L vs. ≥ 100 g/L)	2.769 (1.043∼7.351)	0.041
Ca (<12 mg/dL vs. ≥ 12 mg/dL)	1.143 (0.554∼2.356)	0.718
ALB (<35 g/L vs. ≥ 35 g/L)	2.224 (0.982∼5.040)	0.055
β2-MG (≥5.5 mg/L vs. < 5.5 mg/L)	2.857 (1.354∼6.028)	0.006
LDH (≥220 U/L vs. < 220 U/L)	2.513 (1.206∼5.238)	0.014
t (4; 14) (yes vs. no)	2.902 (1.132∼7.436)	0.027
t (14; 16) (yes vs. no)	3.040 (1.053∼8.775)	0.040
Del (17p) (yes vs. no)	1.978 (0.753∼5.193)	0.166
ISS stage (per stage)	2.360 (1.318∼4.225)	0.004
R-ISS stage (per stage)	3.293 (1.710∼6.341)	<0.001
Multivariable Cox regression model
PHF19 expression post induction treatment (abnormal vs. normal)	2.474 (1.190∼5.145)	0.015
Age (≥65 years vs. < 65 years)	2.601 (1.192∼5.673)	0.016
β2-MG (≥5.5 mg/L vs. < 5.5 mg/L)	3.125 (1.449∼6.738)	0.004

EFS, event-free survival; HR, hazard ratio; CI, confidence interval; PHF19, PHD finger protein 19; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; Ca, calcium; ALB, albumin; β₂-MG, beta-2-microglobulin; LDH, lactate dehydrogenase; ISS, international staging system; R-ISS, revised international staging system.

Table 4. Cox regression model of OS.

Items	HR (95% CI)	P value
Univariable Cox regression model
PHF19 expression at baseline (abnormal vs. normal)	3.104 (1.081∼8.907)	0.035
PHF19 expression post induction treatment (abnormal vs. normal)	3.404 (1.290∼8.984)	0.013
Age (≥65 years vs. < 65 years)	2.829 (0.989∼8.092)	0.052
Gender (female vs. male)	1.620 (0.623∼4.212)	0.323
Immunoglobulin subtype
Others (reference)
(IgG vs. reference)	1.834 (0.496∼6.778)	0.363
(IgA vs. reference)	3.683 (0.853∼15.894)	0.081
Bone lesion (yes vs. no)	1.980 (0.567∼6.910)	0.284
Renal impairment (yes vs. no)	3.631 (1.243∼10.605)	0.018
Hb (<100 g/L vs. ≥ 100 g/L)	3.973 (0.900∼17.543)	0.069
Ca (<12 mg/dL vs. ≥ 12 mg/dL)	1.229 (0.474∼3.188)	0.671
ALB (<35 g/L vs. ≥ 35 g/L)	2.816 (0.872∼9.088)	0.083
β2-MG (≥5.5 mg/L vs. < 5.5 mg/L)	5.401 (1.748∼16.684)	0.003
LDH (≥220 U/L vs. < 220 U/L)	1.680 (0.616∼4.578)	0.311
t (4; 14) (yes vs. no)	5.895 (1.828∼19.011)	0.003
t (14; 16) (yes vs. no)	1.591 (0.358∼7.066)	0.542
Del (17p) (yes vs. no)	1.977 (0.566∼6.904)	0.286
ISS stage (per stage)	3.526 (1.439∼8.636)	0.006
R-ISS stage (per stage)	3.914 (1.662∼9.221)	0.002
Multivariable Cox regression model
PHF19 expression post induction treatment (abnormal vs. normal)	3.124 (1.056∼9.244)	0.040
Age (≥65 years vs. < 65 years)	4.394 (1.398∼13.813)	0.011
β2-MG (≥5.5 mg/L vs. < 5.5 mg/L)	6.157 (1.857∼20.409)	0.003
t (4; 14) (yes vs. no)	3.910 (1.137∼13.445)	0.031

OS, overall survival; HR, hazard ratio; CI, confidence interval; PHF19, PHD finger protein 19; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; Ca, calcium; ALB, albumin; β₂-MG, beta-2-microglobulin; LDH, lactate dehydrogenase; ISS, international staging system; R-ISS, revised international staging system.