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://www.thejh.org

Original Article

Volume 12, Number 6, December 2023, pages 243-254

Impact of Cytogenetic Abnormalities, Induction and Maintenance Regimens on Outcomes After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma: A Decade-Long Real-World Experience

Figure 5. Progression-free survival (a) and overall survival (b) based on proteasome inhibitor vs. non-proteasome inhibitor-based maintenance.

**Table 1.** Patient, Disease, and Response Characteristics
Characteristics	High-risk cytogenetics (N = 73)	Standard-risk cytogenetics (N = 363)	P value
^aPercentages may total greater than 100% as patients may have more than one cytogenetic abnormality. ^bP value for RVd vs. other. ^cP value is for lenalidomide alone vs. other maintenance regimens. *P < 0.05. RVD: lenalidomide - bortezomib - dexamethasone; Dara-RVD: daratumumab - lenalidomide - bortezomib - dexamethasone; CyBorD: cyclophosphamide - bortezomib - dexamethasone; Ig: immunoglobulin; ECOG: Eastern Cooperative Oncology Group; ISS: International Staging System; HCT-CI: hematopoietic cell transplantation comorbidity index; PI: proteasome inhibitor; sCR/CR: stringent complete response/complete response; VGPR: very good partial response; PR: partial response; SD: stable disease; PD: progressive disease.
Median age, years (range)
At diagnosis	60 (29 - 77)	60 (21 - 81)	0.86
At ASCT	62 (31 - 79)	62 (25 - 81)	0.71
Age > 65, n (%)	17 (23)	93 (26)	0.68
Sex, n (%)
Male	39 (55)	203 (56)	0.70
Female	34 (45)	160 (44)
Race/ethnicity, n (%)
Non-Hispanic White	46 (61)	213 (82)	0.51
Non-Hispanic Black	27 (36)	161 (42)
Other	2 (3)	6 (2)
Body mass index, n (%)
< 30 kg/m²	40 (55)	199 (55)	0.72
≥ 30 kg/m²	33 (45)	164 (45)
Subtype, n (%)
IgG	39 (53)	230 (63)
IgA	23 (32)	63 (18)	0.05
Light chain only	9 (12)	59 (163)
Non-secretory	2 (3)	11 (3)
Other
Durie-Salmon Staging System (DSS), n (%)
I	6 (8)	33 (9)
II	10 (14)	63 (17)
III	30 (41)	107 (30)	0.02*
Unknown	27 (37)	160 (44)
International Staging System (ISS), n (%)
I	8 (10)	104 (29)
II	18 (25)	87 (24)
III	18 (25)	86 (24)	0.10
Unknown	29 (40)	86 (23)
Revised International Staging System (R-ISS), n (%)
I	4 (5)	52 (14)
II	12 (16)	51 (14)	< 0.001*
III	15 (21)	19 (6)
Unknown	42 (58)	241 (66)
ECOG performance status, n (%)
0	10 (14)	63 (17)
1	59 (81)	287 (79)	0.17
2+	4 (5)	7 (2)
Missing	0	6 (2)
Cytogenetic abnormalities^a, n (%)
Del 17p	36 (48)	0
t4;14	34 (45)	0
t14;16	6 (1)	0	< 0.001*
t14;20	1 (1)	2 (1)
Amp 1q	3 (4)	0
Gain 1q	33 (44)	89 (24)
HCT-CI, n (%)
0 - 1	17 (35)	94 (40)
2 - 3	15 (31)	92 (39)	0.097
4+	17 (35)	48 (21)
sCr > 2 or CrCl < 60 mL/min/1.73 m² at ASCT, n (%)
Yes	13 (18)	53 (14)
No	44 (60)	264 (73)
Missing	16 (22)	46 (13)	0.27
Melphalan dose, n (%)
200 mg/m²	52 (71)	286 (79)
140 mg/m²	21 (29)	77 (21)	0.16
Induction regimen, n (%)^b
RVd	29 (39)	207 (57)
Dara-RVd	6 (8)	26 (7)
CyBordD	1 (3)	76 (21)	0.01*
Carfilzomib-based	9 (11)	23 (6)
Other	28 (39)	31 (9)
Maintenance regimen, n (%)^c
Lenalidomide	37 (51)	264 (72)
Lenalidomide + PI	19 (26)	26 (7)
Lenalidomide + daratumumab	4 (5)	13 (4)	< 0.001*
PI only	2 (4)	13 (4)
Other	4 (5)	4 (1)
None	7 (9)	43 (12)
Best overall response post ASCT, n (%)
sCR/CR	33 (45)	161 (44)
VGPR	29 (39)	140 (38)
PR	4 (5)	47 (13)	0.01*
SD	4 (5)	3 (1)
PD	3 (5)	4 (1)
Response prior to ASCT, n (%)
sCR/CR	11 (15)	61 (17)
VGPR	27 (37)	155 (44)
PR	32 (44)	135 (37)	0.34
SD	3 (4)	5 (1)
PD	0 (0)	4 (1)
Response at day +100 post ASCT, n (%)
sCR/CR	29 (40)	115 (32)
VGPR	34 (47)	161 (44)
PR	3 (4)	59 (16)
SD	1 (1)	3 (1)	0.09
PD	2 (3)	7 (7)
Response at 2-years post ASCT, n (%)
sCR/CR	14 (19)	82 (23)
VGPR	9 (12)	61 (17)
PR	1 (1)	21 (6)	0.16
SD	2 (3)	11 (3)
PD	15 (21)	45 (12)

Table 1. Patient, Disease, and Response Characteristics

Characteristics

High-risk cytogenetics (N = 73)

Standard-risk cytogenetics (N = 363)

P value

^aPercentages may total greater than 100% as patients may have more than one cytogenetic abnormality. ^bP value for RVd vs. other. ^cP value is for lenalidomide alone vs. other maintenance regimens. *P < 0.05. RVD: lenalidomide - bortezomib - dexamethasone; Dara-RVD: daratumumab - lenalidomide - bortezomib - dexamethasone; CyBorD: cyclophosphamide - bortezomib - dexamethasone; Ig: immunoglobulin; ECOG: Eastern Cooperative Oncology Group; ISS: International Staging System; HCT-CI: hematopoietic cell transplantation comorbidity index; PI: proteasome inhibitor; sCR/CR: stringent complete response/complete response; VGPR: very good partial response; PR: partial response; SD: stable disease; PD: progressive disease.

Median age, years (range)

At diagnosis

60 (29 - 77)

60 (21 - 81)

0.86

At ASCT

62 (31 - 79)

62 (25 - 81)

0.71

Age > 65, n (%)

17 (23)

93 (26)

0.68

Sex, n (%)

Male

39 (55)

203 (56)

0.70

Female

34 (45)

160 (44)

Race/ethnicity, n (%)

Non-Hispanic White

46 (61)

213 (82)

0.51

Non-Hispanic Black

27 (36)

161 (42)

Other

2 (3)

6 (2)

Body mass index, n (%)

< 30 kg/m²

40 (55)

199 (55)

0.72

≥ 30 kg/m²

33 (45)

164 (45)

Subtype, n (%)

IgG

39 (53)

230 (63)

IgA

23 (32)

63 (18)

0.05

Light chain only

9 (12)

59 (163)

Non-secretory

2 (3)

11 (3)

Other

Durie-Salmon Staging System (DSS), n (%)

6 (8)

33 (9)

10 (14)

63 (17)

III

30 (41)

107 (30)

0.02*

Unknown

27 (37)

160 (44)

International Staging System (ISS), n (%)

8 (10)

104 (29)

18 (25)

87 (24)

III

18 (25)

86 (24)

0.10

Unknown

29 (40)

86 (23)

Revised International Staging System (R-ISS), n (%)

4 (5)

52 (14)

12 (16)

51 (14)

< 0.001*

III

15 (21)

19 (6)

Unknown

42 (58)

241 (66)

ECOG performance status, n (%)

10 (14)

63 (17)

59 (81)

287 (79)

0.17

4 (5)

7 (2)

Missing

6 (2)

Cytogenetic abnormalities^a, n (%)

Del 17p

36 (48)

t4;14

34 (45)

t14;16

6 (1)

< 0.001*

t14;20

1 (1)

2 (1)

Amp 1q

3 (4)

Gain 1q

33 (44)

89 (24)

HCT-CI, n (%)

0 - 1

17 (35)

94 (40)

2 - 3

15 (31)

92 (39)

0.097

17 (35)

48 (21)

sCr > 2 or CrCl < 60 mL/min/1.73 m² at ASCT, n (%)

Yes

13 (18)

53 (14)

44 (60)

264 (73)

Missing

16 (22)

46 (13)

0.27

Melphalan dose, n (%)

200 mg/m²

52 (71)

286 (79)

140 mg/m²

21 (29)

77 (21)

0.16

Induction regimen, n (%)^b

RVd

29 (39)

207 (57)

Dara-RVd

6 (8)

26 (7)

CyBordD

1 (3)

76 (21)

0.01*

Carfilzomib-based

9 (11)

23 (6)

Other

28 (39)

31 (9)

Maintenance regimen, n (%)^c

Lenalidomide

37 (51)

264 (72)

Lenalidomide + PI

19 (26)

26 (7)

Lenalidomide + daratumumab

4 (5)

13 (4)

< 0.001*

PI only

2 (4)

13 (4)

Other

4 (5)

4 (1)

None

7 (9)

43 (12)

Best overall response post ASCT, n (%)

sCR/CR

33 (45)

161 (44)

VGPR

29 (39)

140 (38)

4 (5)

47 (13)

0.01*

4 (5)

3 (1)

3 (5)

4 (1)

Response prior to ASCT, n (%)

sCR/CR

11 (15)

61 (17)

VGPR

27 (37)

155 (44)

32 (44)

135 (37)

0.34

3 (4)

5 (1)

0 (0)

4 (1)

Response at day +100 post ASCT, n (%)

sCR/CR

29 (40)

115 (32)

VGPR

34 (47)

161 (44)

3 (4)

59 (16)

1 (1)

3 (1)

0.09

2 (3)

7 (7)

Response at 2-years post ASCT, n (%)

sCR/CR

14 (19)

82 (23)

VGPR

9 (12)

61 (17)

1 (1)

21 (6)

0.16

2 (3)

11 (3)

15 (21)

45 (12)

**Table 2.** Survival Outcomes and Response Rates by Factors of Cytogenetic Risk Profile, Induction, and Maintenance Regimen
	PFS, median months (range)	P value	OS, median months (range)	P value	Best ORR, %	P value	Overall VGPR, %	P value
Cytogenetics
High-risk	29 (1 - 100)	< 0.001*	70 (1 - 101)	0.13	90	0.01	85	0.67
Standard-risk	58 (1 - 123)		NR (1 - 128)		96		83
Standard-risk
With +1q	38 (1 - 123)	0.01*	60 (1 - 123)	0.01*	98	0.64	82	0.84
Without +1q	76(1 - 122)		NR (1 - 128)		96		83
Induction regimen
Lenalidomide-based	53 (1 - 112)	0.05*	NR (1 - 112)	0.02*	96	0.41	84	0.09
Non-lenalidomide-based	39 (1 - 123)		78(1 - 123)		94		83
Maintenance regimen
Lenalidomide-based	53 (1 - 123)	0.003*	104	0.02*	98	< 0.001*	87	0.16
Non-lenalidomide-based	38 (2 - 91)		NR		91		86
Maintenance regimen
PI-based	54 (11 - 97)	0.43	NR	0.82	94	0.23	86	0.054
Non-PI-based	46 (37 - 55)		92 (NR)		89		76

Table 2. Survival Outcomes and Response Rates by Factors of Cytogenetic Risk Profile, Induction, and Maintenance Regimen

PFS, median months (range)

P value

OS, median months (range)

P value

Best ORR, %

P value

Overall VGPR, %

P value

Cytogenetics

High-risk

29 (1 - 100)

< 0.001*

70 (1 - 101)

0.13

0.01

0.67

Standard-risk

58 (1 - 123)

NR (1 - 128)

Standard-risk

With +1q

38 (1 - 123)

0.01*

60 (1 - 123)

0.01*

0.64

0.84

Without +1q

76(1 - 122)

NR (1 - 128)

Induction regimen

Lenalidomide-based

53 (1 - 112)

0.05*

NR (1 - 112)

0.02*

0.41

0.09

Non-lenalidomide-based

39 (1 - 123)

78(1 - 123)

Maintenance regimen

Lenalidomide-based

53 (1 - 123)

0.003*

104

0.02*

< 0.001*

0.16

Non-lenalidomide-based

38 (2 - 91)

Maintenance regimen

PI-based

54 (11 - 97)

0.43

0.82

0.23

0.054

Non-PI-based

46 (37 - 55)

92 (NR)

**Table 3.** Univariate Analysis of Factors Associated With PFS and OS
Univariate analysis	PFS HR (95% CI)	OS HR (95% CI)
ISS: International Staging System; PFS: progression-free survival; OS: overall survival; HCT-CI: hematopoietic cell transplantation specific comorbidity index; HR: hazard ratio; CI: confidence interval.
Cytogenetic risk profile: high-risk	2.085 (1.483 - 2.931)	1.421 (0.897 - 2.252)
Presence of +1q abnormality	0.761 (0.417 - 1.387)	1.250 (0.618 - 2.532)
ISS II/III	1.183 (0.881 - 1.588)	1.197 (0.821 - 1.743)
Lenalidomide-based induction	0.740 (0.550 - 0.996)	0.628 (0.430 - 0.919)
Melphalan 200 mg/m²	0.797 (0.566 - 1.123)	0.786 (0.512 - 1.207)
Proteasome inhibitor-based maintenance	0.852 (0.572 - 1.271)	0.942 (0.571 - 1.554)
Lenalidomide-based maintenance	0.426 (0.318 - 0.570)	0.376 (0.263 - 0.538)
Age > 65	1.068 (0.801 - 1.423)	1.064 (0.738 - 1.535)
Race/ethnicity: White vs. African American	0.955 (0.718 - 1.269)	1.018 (0.711 - 1.456)
HCT-CI 3+	0.823 (0.478 - 1.416)	1.053 (0.481 - 2.306)

Table 3. Univariate Analysis of Factors Associated With PFS and OS

Univariate analysis

PFS HR (95% CI)

OS HR (95% CI)

ISS: International Staging System; PFS: progression-free survival; OS: overall survival; HCT-CI: hematopoietic cell transplantation specific comorbidity index; HR: hazard ratio; CI: confidence interval.

Cytogenetic risk profile: high-risk

2.085 (1.483 - 2.931)

1.421 (0.897 - 2.252)

Presence of +1q abnormality

0.761 (0.417 - 1.387)

1.250 (0.618 - 2.532)

ISS II/III

1.183 (0.881 - 1.588)

1.197 (0.821 - 1.743)

Lenalidomide-based induction

0.740 (0.550 - 0.996)

0.628 (0.430 - 0.919)

Melphalan 200 mg/m²

0.797 (0.566 - 1.123)

0.786 (0.512 - 1.207)

Proteasome inhibitor-based maintenance

0.852 (0.572 - 1.271)

0.942 (0.571 - 1.554)

Lenalidomide-based maintenance

0.426 (0.318 - 0.570)

0.376 (0.263 - 0.538)

Age > 65

1.068 (0.801 - 1.423)

1.064 (0.738 - 1.535)

Race/ethnicity: White vs. African American

0.955 (0.718 - 1.269)

1.018 (0.711 - 1.456)

HCT-CI 3+

0.823 (0.478 - 1.416)

1.053 (0.481 - 2.306)

**Table 4.** Multivariate Analysis of Factors Associated With PFS and OS
Multivariate analysis	PFS HR (95% CI)	OS HR (95% CI)
ISS: International Staging System; PFS: progression-free survival; OS: overall survival; HCT-CI: hematopoietic cell transplantation specific comorbidity index; HR: hazard ratio; CI: confidence interval.
Cytogenetic risk profile: high-risk	0.285 (0.142 - 0.572)	0.699 (0.218 - 2.236)
Presence of +1q abnormality	1.682 (0.922 - 3.068)	1.916 (0.752 - 4.881)
ISS II/III	1.628 (0.854 - 3.102)	1.266 (0.467 - 3.433)
Lenalidomide-based induction	1.502 (0.681 - 3.310)	1.447 (0.427 - 4.910)
Melphalan 200 mg/m²	1.110 (0.493 - 2.500)	1.727 (0.464 - 6.428)
Proteasome inhibitor-based maintenance	0.191 (0.072 - 0.508)	0.306 (0.077 - 1.209)
Lenalidomide-based maintenance	0.267 (0.118 - 0.606)	0.158 (0.054 - 0.458)
Age > 65	2.280 (1.162 - 4.474)	1.848 (0.642 - 5.317)
Race/ethnicity: White vs. African American	0.815 (0.434 - 1.531)	1.123 (0.424 - 2.973)
HCT-CI 3+	0.653 (0.301 - 1.416)	1.169 (0.391 - 3.492)

Table 4. Multivariate Analysis of Factors Associated With PFS and OS

Multivariate analysis

PFS HR (95% CI)

OS HR (95% CI)

Cytogenetic risk profile: high-risk

0.285 (0.142 - 0.572)

0.699 (0.218 - 2.236)

Presence of +1q abnormality

1.682 (0.922 - 3.068)

1.916 (0.752 - 4.881)

ISS II/III

1.628 (0.854 - 3.102)

1.266 (0.467 - 3.433)

Lenalidomide-based induction

1.502 (0.681 - 3.310)

1.447 (0.427 - 4.910)

Melphalan 200 mg/m²

1.110 (0.493 - 2.500)

1.727 (0.464 - 6.428)

Proteasome inhibitor-based maintenance

0.191 (0.072 - 0.508)

0.306 (0.077 - 1.209)

Lenalidomide-based maintenance

0.267 (0.118 - 0.606)

0.158 (0.054 - 0.458)

Age > 65

2.280 (1.162 - 4.474)

1.848 (0.642 - 5.317)

Race/ethnicity: White vs. African American

0.815 (0.434 - 1.531)

1.123 (0.424 - 2.973)

HCT-CI 3+

0.653 (0.301 - 1.416)

1.169 (0.391 - 3.492)