J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://jh.elmerpub.com

Original Article

Volume 15, Number 3, June 2026, pages 144-155

Prognostic Significance of Isolated Beta 2-Microglobulin Elevation in Thai Multiple Myeloma: Impact of Renal Function Assessment

↓ Figure 1. Best treatment response following induction therapy. Stacked bar chart illustrating the distribution of the best response levels among patients with newly diagnosed multiple myeloma, stratified by prognostic group: group A (standard risk: β2M < 5.5 mg/L), group B (isolated high β2M: β2M ≥ 5.5 mg/L with creatinine < 1.2 mg/dL), and group C (high β2M with renal impairment: β2M ≥ 5.5 mg/L with creatinine ≥ 1.2 mg/dL). Percentages within each bar represent the proportion of patients achieving each response category. Response categories are defined according to IMWG criteria, ranging from sCR to PD. Response data were available for 218 patients. β2M: β₂-microglobulin; sCR: stringent complete response; CR: complete response; VGPR: very good partial response; PR: partial response; SD: stable disease; PD: progressive disease.

↓ Figure 2. Survival outcomes stratified by β2M using serum creatinine– and creatinine clearance–based definitions of renal function. Kaplan–Meier estimates of overall survival (OS) and progression-free survival (PFS) among patients with newly diagnosed multiple myeloma. Panels (a) and (b) show OS and PFS, respectively, stratified by the 2024 IMS–IMWG serum creatinine–based criteria: group A (standard risk: β2M < 5.5 mg/L), group B (isolated high β2M: β2M ≥ 5.5 mg/L with serum creatinine < 1.2 mg/dL), and group C (high β2M with renal impairment: β2M ≥ 5.5 mg/L with serum creatinine ≥ 1.2 mg/dL). Panels (c) and (d) show OS and PFS, respectively, stratified by the creatinine clearance–based definition of renal function: low β2M, high β2M with preserved renal function (CrCl ≥ 60 mL/min), and high β2M with renal impairment (CrCl < 60 mL/min). IMS–IMWG: International Myeloma Society–International Myeloma Working Group; CrCl: creatinine clearance; β2M: β₂-microglobulin.

↓ Figure 3. Reclassification of prognostic groups according to the 2024 IMS–IMWG criteria and the CrCl-based criteria. The Sankey diagram illustrates changes in patient distribution when transitioning from the standard SCr-based definition (left) to a CrCl-based threshold of 60 mL/min (right). Flow colors represent sex (pink for female and blue for male), while nodes indicate prognostic groups defined by β2M and renal function. IMS–IMWG: International Myeloma Society–International Myeloma Working Group; SCr: serum creatinine; CrCl: creatinine clearance; β2M: β₂-microglobulin.

↓ **Table 1.** Baseline Characteristics
Parameter	Total, N = 250 (100%)	Standard risk; group A, N = 109 (43.6%)	Isolated high β2M; group B, N = 29 (11.6%)	High β2M with renal impairment; group C, N = 112 (44.8%)	P value
^aDefined as a response of PR or better. ^bNo specified sites and numbers. SD: standard deviation; IQR: interquartile range; CrCl: creatinine clearance; GFR: glomerular filtration rate; β2M: β₂-microglobulin; sCR: stringent complete response; CR: complete response; VGPR: very good partial response; ORR: objective response rate; PR: partial response; SD: stable disease; PD: progressive disease; ECOG: Eastern Cooperative Oncology Group.
Year of diagnosis, no. (%)
2006–2010	55 (22.00)	23 (21.10)	11 (37.93)	21 (18.75)	0.354
2011–2015	70 (28.00)	35 (31.82)	6 (20.69)	29 (26.13)
2016–2020	102 (40.80)	41 (37.27)	11 (37.93)	50 (45.05)
2021–2023	23 (9.20)	10 (9.09)	1 (3.45)	12 (10.81)
Age, years, ± SD	60.98 ± 12.08	59.89 ± 13.06	62.07 ± 11.64	61.77 ± 11.17	0.451
Sex, no. (%)
Male	155 (62.00)	70 (64.22)	8 (27.59)	77 (68.75)	< 0.001
Female	95 (38.00)	39 (35.78)	21 (72.41)	35 (31.25)
Weight, kg, ± SD	58.88 ± 12.08	60.65 ± 12.32	55.78 ± 10.19	57.96 ± 12.11	0.085
ECOG, no. (%)
0–1	136 (54.40)	71 (65.14)	15 (51.72)	50 (44.64)	0.049
2	74 (29.60)	26 (23.85)	7 (24.14)	41 (36.61)
3	29 (11.60)	8 (7.34)	6 (20.69)	15 (13.39)
4	11 (4.40)	4 (3.67)	1 (3.45)	6 (5.36)
β₂-microglobulin, mg/L (IQR)	5.99 (3.75–12.16)	3.47 (2.40–4.30)	7.17 (5.78–9)	12.64 (8.47–17.57)	< 0.001
Creatinine, mg/dL (IQR)	1.30 (0.90–2.32)	0.92 (0.71–1.10)	0.90 (0.73–0.97)	2.54 (1.57–5.40)	< 0.001
CrCl (Cockcroft-Gault Equation), mL/min (IQR)	47.07 (21.58–68.52)	62.12 (48.94–87.76)	61.62 (47.90–76.50)	19.53 (10.74–35.62)	< 0.001
Estimated GFR (CKD-EPI 2021), mL/min/1.73 m² (IQR)	57.83 (28.24–86.67)	82.90 (65.34–100.30)	84.30 (68.77–96.93)	22.62 (9.41–46.61)	< 0.001
Albumin, mg/dL ± SD, n = 249	3.43 ± 0.78	3.56 ± 0.69	3.27 ± 0.69	3.33 ± 0.86	0.050
High LDH, no. (%), n = 153	58 (37.91)	17 (26.15)	11 (64.71)	30 (42.25)	0.009
High-risk cytogenetics, no. (%)
No detection	42 (16.80)	19 (17.43)	7 (24.14)	16 (14.29)	0.457
t(4:14)	6 (2.40)	2 (1.83)	0 (0.00)	4 (3.57)
Del(17p)	7 (2.80)	1 (0.92)	1 (3.45)	5 (4.46)
Not done	195 (78.00)	87 (79.82)	21 (72.41)	87 (77.68)
International Staging System (ISS), no. (%)
Stage I	35 (14.00)	35 (32.11)	0 (0.00)	0 (0.00)	< 0.001
Stage II	74 (29.60)	74 (67.89)	0 (0.00)	0 (0.00)
Stage III	141 (56.40)	0 (0.00)	29 (100.00)	112 (100.00)
Hemoglobin, g/dL (IQR)	8.9 (7.5–10.2)	9.6 (8–11)	9.2 (8–9.7)	8.2 (6.9–9.4)	< 0.001
Calcium, mg/dL (IQR)	9.54 (9–10.69)	9.37 (8.91–9.75)	9.25 (8.8–9.6)	10.1 (9.13–11.9)	< 0.001
Induction regimen, no. (%)
Bortezomib-based	126 (50.40)	52 (47.71)	8 (27.59)	66 (58.59)	0.008
Thalidomide-based	72 (28.80)	30 (27.52)	12 (41.38)	30 (26.79)	0.282
Lenalidomide-based	5 (2.00)	4 (3.67)	0 (0.00)	1 (0.89)	0.260
Daratumumab-based	1 (0.40)	0 (0.00)	0 (0.00)	1 (0.89)	1.000
Type of induction regimen, no. (%)
Palliative care/steroid monotherapy	15 (6.00)	7 (6.42)	2 (6.90)	6 (5.36)	0.122
Doublet	84 (33.60)	31 (28.44)	16 (55.17)	37 (33.04)
Triplet	130 (52.00)	58 (53.21)	10 (34.48)	62 (55.36)
Quadruplet	1 (0.40)	0 (0.00)	0 (0.00)	1(0.89)
Chemotherapy	20 (8.00)	13 (11.93)	1 (3.45)	6 (5.36)
Best response after induction, no. (%), n = 218
sCR	31 (14.22)	12 (12.24)	2 (8.33)	17 (17.71)	0.388
CR	51 (23.39)	26 (26.53)	7 (29.17)	18 (18.75)
VGPR	47 (21.56)	23 (23.47)	1 (4.17)	23 (23.96)
PR	57 (26.15)	25 (25.51)	10 (41.67)	22 (22.92)
SD	25 (11.47)	9 (9.18)	3 (12.50)	13 (13.54)
PD	7 (3.21)	3 (3.06)	1 (4.17)	3 (3.13)
ORR^a, no. (%), n = 218	186 (85.32)	86 (87.76)	20 (83.33)	80 (83.33)	0.630
Plasmacytoma^b, no. (%)	83 (33.20)	41 (37.61)	12 (41.38)	30 (26.79)	0.141
ASCT, no. (%)	86 (34.40)	42 (38.53)	7 (24.14)	37 (33.04)	0.346
Mortality, no. (%)	89 (35.60)	32 (29.36)	11 (37.93)	46 (41.07)	0.192

↓ Table 1. Baseline Characteristics

Parameter

Total, N = 250 (100%)

Standard risk; group A, N = 109 (43.6%)

Isolated high β2M; group B, N = 29 (11.6%)

High β2M with renal impairment; group C, N = 112 (44.8%)

P value

^aDefined as a response of PR or better. ^bNo specified sites and numbers. SD: standard deviation; IQR: interquartile range; CrCl: creatinine clearance; GFR: glomerular filtration rate; β2M: β₂-microglobulin; sCR: stringent complete response; CR: complete response; VGPR: very good partial response; ORR: objective response rate; PR: partial response; SD: stable disease; PD: progressive disease; ECOG: Eastern Cooperative Oncology Group.

Year of diagnosis, no. (%)

2006–2010

55 (22.00)

23 (21.10)

11 (37.93)

21 (18.75)

0.354

2011–2015

70 (28.00)

35 (31.82)

6 (20.69)

29 (26.13)

2016–2020

102 (40.80)

41 (37.27)

11 (37.93)

50 (45.05)

2021–2023

23 (9.20)

10 (9.09)

1 (3.45)

12 (10.81)

Age, years, ± SD

60.98 ± 12.08

59.89 ± 13.06

62.07 ± 11.64

61.77 ± 11.17

0.451

Sex, no. (%)

Male

155 (62.00)

70 (64.22)

8 (27.59)

77 (68.75)

< 0.001

Female

95 (38.00)

39 (35.78)

21 (72.41)

35 (31.25)

Weight, kg, ± SD

58.88 ± 12.08

60.65 ± 12.32

55.78 ± 10.19

57.96 ± 12.11

0.085

ECOG, no. (%)

0–1

136 (54.40)

71 (65.14)

15 (51.72)

50 (44.64)

0.049

74 (29.60)

26 (23.85)

7 (24.14)

41 (36.61)

29 (11.60)

8 (7.34)

6 (20.69)

15 (13.39)

11 (4.40)

4 (3.67)

1 (3.45)

6 (5.36)

β₂-microglobulin, mg/L (IQR)

5.99 (3.75–12.16)

3.47 (2.40–4.30)

7.17 (5.78–9)

12.64 (8.47–17.57)

< 0.001

Creatinine, mg/dL (IQR)

1.30 (0.90–2.32)

0.92 (0.71–1.10)

0.90 (0.73–0.97)

2.54 (1.57–5.40)

< 0.001

CrCl (Cockcroft-Gault Equation), mL/min (IQR)

47.07 (21.58–68.52)

62.12 (48.94–87.76)

61.62 (47.90–76.50)

19.53 (10.74–35.62)

< 0.001

Estimated GFR (CKD-EPI 2021), mL/min/1.73 m² (IQR)

57.83 (28.24–86.67)

82.90 (65.34–100.30)

84.30 (68.77–96.93)

22.62 (9.41–46.61)

< 0.001

Albumin, mg/dL ± SD, n = 249

3.43 ± 0.78

3.56 ± 0.69

3.27 ± 0.69

3.33 ± 0.86

0.050

High LDH, no. (%), n = 153

58 (37.91)

17 (26.15)

11 (64.71)

30 (42.25)

0.009

High-risk cytogenetics, no. (%)

No detection

42 (16.80)

19 (17.43)

7 (24.14)

16 (14.29)

0.457

t(4:14)

6 (2.40)

2 (1.83)

0 (0.00)

4 (3.57)

Del(17p)

7 (2.80)

1 (0.92)

1 (3.45)

5 (4.46)

Not done

195 (78.00)

87 (79.82)

21 (72.41)

87 (77.68)

International Staging System (ISS), no. (%)

Stage I

35 (14.00)

35 (32.11)

0 (0.00)

< 0.001

Stage II

74 (29.60)

74 (67.89)

0 (0.00)

Stage III

141 (56.40)

0 (0.00)

29 (100.00)

112 (100.00)

Hemoglobin, g/dL (IQR)

8.9 (7.5–10.2)

9.6 (8–11)

9.2 (8–9.7)

8.2 (6.9–9.4)

< 0.001

Calcium, mg/dL (IQR)

9.54 (9–10.69)

9.37 (8.91–9.75)

9.25 (8.8–9.6)

10.1 (9.13–11.9)

< 0.001

Induction regimen, no. (%)

Bortezomib-based

126 (50.40)

52 (47.71)

8 (27.59)

66 (58.59)

0.008

Thalidomide-based

72 (28.80)

30 (27.52)

12 (41.38)

30 (26.79)

0.282

Lenalidomide-based

5 (2.00)

4 (3.67)

0 (0.00)

1 (0.89)

0.260

Daratumumab-based

1 (0.40)

0 (0.00)

1 (0.89)

1.000

Type of induction regimen, no. (%)

Palliative care/steroid monotherapy

15 (6.00)

7 (6.42)

2 (6.90)

6 (5.36)

0.122

Doublet

84 (33.60)

31 (28.44)

16 (55.17)

37 (33.04)

Triplet

130 (52.00)

58 (53.21)

10 (34.48)

62 (55.36)

Quadruplet

1 (0.40)

0 (0.00)

1(0.89)

Chemotherapy

20 (8.00)

13 (11.93)

1 (3.45)

6 (5.36)

Best response after induction, no. (%), n = 218

sCR

31 (14.22)

12 (12.24)

2 (8.33)

17 (17.71)

0.388

51 (23.39)

26 (26.53)

7 (29.17)

18 (18.75)

VGPR

47 (21.56)

23 (23.47)

1 (4.17)

23 (23.96)

57 (26.15)

25 (25.51)

10 (41.67)

22 (22.92)

25 (11.47)

9 (9.18)

3 (12.50)

13 (13.54)

7 (3.21)

3 (3.06)

1 (4.17)

3 (3.13)

ORR^a, no. (%), n = 218

186 (85.32)

86 (87.76)

20 (83.33)

80 (83.33)

0.630

Plasmacytoma^b, no. (%)

83 (33.20)

41 (37.61)

12 (41.38)

30 (26.79)

0.141

ASCT, no. (%)

86 (34.40)

42 (38.53)

7 (24.14)

37 (33.04)

0.346

Mortality, no. (%)

89 (35.60)

32 (29.36)

11 (37.93)

46 (41.07)

0.192

↓ **Table 2.** Univariable and Multivariable Cox Regression Analyses for Overall Survival and Progression-Free Survival Stratified by β2M and SCr
Prognostic group	Overall survival	Progression-free survival
^aAdjusted for age, sex, bortezomib-based regimens, ASCT status, Eastern Cooperative Oncology Group performance status (≥ 2), and presence of plasmacytoma. HR: hazard ratio; CI: confidence interval; β2M: β₂-microglobulin; SCr: serum creatinine; ASCT: autologous stem cell transplantation.
Group A (standard)	1.00 (Ref)	-	1.00 (Ref)	-	1.00 (Ref)	-	1.00 (Ref)	-
Group B (isolated high β2M)	1.64 (0.82–3.26)	0.159	1.51 (0.70–3.24)	0.291	1.53 (0.98–2.39)	0.064	1.37 (0.86–2.20)	0.187
Group C (high β2M and impaired renal function)	1.96 (1.24–3.09)	0.004	1.79 (1.11–2.86)	0.016	1.38 (1.03–1.85)	0.033	1.31 (0.96–1.79)	0.091
Comparison group B vs. C	0.84 (0.43–1.62)	0.596	0.85 (0.40–1.81)	0.667	1.11 (0.71–1.73)	0.647	1.05 (0.64–1.71)	0.851

↓ Table 2. Univariable and Multivariable Cox Regression Analyses for Overall Survival and Progression-Free Survival Stratified by β2M and SCr

Prognostic group

Overall survival

Progression-free survival

Crude HR (95% CI)

Adjusted HR (95% CI)^a

Crude HR (95% CI)

Adjusted HR (95% CI)^a

^aAdjusted for age, sex, bortezomib-based regimens, ASCT status, Eastern Cooperative Oncology Group performance status (≥ 2), and presence of plasmacytoma. HR: hazard ratio; CI: confidence interval; β2M: β₂-microglobulin; SCr: serum creatinine; ASCT: autologous stem cell transplantation.

Group A (standard)

1.00 (Ref)

Group B (isolated high β2M)

1.64 (0.82–3.26)

0.159

1.51 (0.70–3.24)

0.291

1.53 (0.98–2.39)

0.064

1.37 (0.86–2.20)

0.187

Group C (high β2M and impaired renal function)

1.96 (1.24–3.09)

0.004

1.79 (1.11–2.86)

0.016

1.38 (1.03–1.85)

0.033

1.31 (0.96–1.79)

0.091

Comparison group B vs. C

0.84 (0.43–1.62)

0.596

0.85 (0.40–1.81)

0.667

1.11 (0.71–1.73)

0.647

1.05 (0.64–1.71)

0.851

↓ **Table 3.** Univariable and Multivariable Cox Regression Analyses for Overall Survival and Progression-Free Survival Stratified by β2M and CrCl
Prognostic group	Overall survival	Progression-free survival
^aAdjusted for age, sex, bortezomib-based regimens, ASCT status, Eastern Cooperative Oncology Group performance status (≥ 2), and presence of plasmacytoma. HR: hazard ratio; CI: confidence interval; β2M: β₂-microglobulin; CrCl: creatinine clearance; ASCT: autologous stem cell transplantation.
Group A (standard)	1.00 (Ref)	-	1.00 (Ref)	-	1.00 (Ref)	-	1.00 (Ref)	-
Group B (isolated high β2M)	2.23 (1.02–4.88)	0.044	2.61 (1.17–5.86)	0.020	1.47 (0.85–2.55)	0.172	1.39 (0.80–2.44)	0.243
Group C (high β2M and impaired renal function)	1.84 (1.17– 2.88)	0.008	1.63 (1.02–2.59)	0.040	1.40 (1.05–1.86)	0.023	1.31 (0.97–1.79)	0.078
Comparison group B vs. C	1.21 (0.57–2.57)	0.612	1.61 (0.73–3.53)	0.239	1.05 (0.61– 1.81)	0.857	1.06 (0.60–1.86)	0.835

↓ Table 3. Univariable and Multivariable Cox Regression Analyses for Overall Survival and Progression-Free Survival Stratified by β2M and CrCl

Prognostic group

Overall survival

Progression-free survival

Crude HR (95% CI)

Adjusted HR (95% CI)^a

Crude HR (95% CI)

Adjusted HR (95% CI)^a

^aAdjusted for age, sex, bortezomib-based regimens, ASCT status, Eastern Cooperative Oncology Group performance status (≥ 2), and presence of plasmacytoma. HR: hazard ratio; CI: confidence interval; β2M: β₂-microglobulin; CrCl: creatinine clearance; ASCT: autologous stem cell transplantation.

Group A (standard)

1.00 (Ref)

Group B (isolated high β2M)

2.23 (1.02–4.88)

0.044

2.61 (1.17–5.86)

0.020

1.47 (0.85–2.55)

0.172

1.39 (0.80–2.44)

0.243

Group C (high β2M and impaired renal function)

1.84 (1.17– 2.88)

0.008

1.63 (1.02–2.59)

0.040

1.40 (1.05–1.86)

0.023

1.31 (0.97–1.79)

0.078

Comparison group B vs. C

1.21 (0.57–2.57)

0.612

1.61 (0.73–3.53)

0.239

1.05 (0.61– 1.81)

0.857

1.06 (0.60–1.86)

0.835