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Table 1 Summary of data from the main phase 3 studies with proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies

From: The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

Study

Arms

N

Doses and schedule

Follow-up (months)

Prior lines

PFS

(months)

ORR (%)

≥CR (%)

OS

(months)

>G3 AE (%)

ASPIRE [19]

KRd vs. Rd

792

K, 20/27mg/m2 BIW; R,

25 mg PO, days 1 and 21;

28-days cycle/s.

67.1

2 (1-3)

26.3 vs. 17.6

HR 0,690

87.1 vs. 66.7

OR 3.472

31.8 vs. 9.3

48.3 vs. 40.4

HR 0.794

87 vs. 83.3

AH, 6.4 vs. 2.3

CF, 4.3 vs. 2.1

ENDEAVOR [11]

Kd vs. Vd

929

K, 20/56 g/m2 I IV, BIW, 28-days cycle; V, 1.3mg/m2 SC/IV, BIW

21-days cycle/s.

12

2 (1-3)

18.7 vs. 9.4

HR 0.533

76.9 vs. 62.6

OR 2.032

13 vs. 6

47.6 vs. 40

HR 0.791

An, 14 vs. 10

AH, 9 vs. 3

NP, 2 vs. 8

IKEMA [50]

IsaKd vs. Kd

302

Isa, 10mg/kg QW for 4w,

then given Q2W; 28-days cycle/s.

20.7

2 (1-3)

NR vs. 19.15

HR 0.531

86.6 vs. 82.9 P 0.19

39.7 vs. 27.6

NA

76.8 vs. 67.2

CANDOR [51]

DKd vs. Kd

466

D, 8mg/kg IV, days 1-2 of cycle 1; 16 mg/kg QW, days 8, 15 and 22 first 2 cycles, then Q2W, cycles 3-6 and every Q4W thereafter; 28-days cycle/s.

17

2 (1-3)

NR vs. 15·8 HR 0.63

84 vs. 75

OR 1.9

29 vs. 10

(MRD,

18 vs. 4)

NA

82 vs. 74

TP, 24 vs. 16

AH, 18 vs. 13

Inf, 33 vs. 18

CF, 5 vs. 11

ARROW [16]

K QW vs. BIW

478

K, 20/70mg/m2 QW vs. 20/27mg/m2 BIW; 28-days cycle.

12.6 / 12

2 (46% vs. 64%)

3 (59% vs. 67%)

11.2 vs. 7.6

HR 0.69

62.9 vs. 40.8

OR 2.68

7 vs. 2

NM

68 vs. 62

CF, 3 vs. 4

ARROW2

(NCT03859427)

KRd QW vs. BIW

460

K, 20/ 56mg/m2 QW vs. 20/27mg/m2 BIW; 28-days cycle/s.

NM

1-3

NAa

NM

NM

NM

NM

MM 003 [52]

Pd vs. d

455

P, 4mg PO, days 1 and 21; 28-days cycle/s.

10

>2

(94.5% pts)

4 vs. 1.9

HR 0.48

31 vs. 10

1 vs. 0

12.7 vs. 8

HR 0.74

88.7 vs. 84.7

ICARIA-MM [10]

IsaPd vs. Pd

307

Pd ± Isa IV 10mg/kg, days 1, 8, 15, and 22 in cycle 1; days 1 and 15 in subsequent cycles; 28-days cycle/s.

11.6

≥2

11.53 vs. 6.47

HR 0.596

60.4 vs. 35.3

5 vs. 1b

NR

87 vs. 71

NP, 60.5 vs. 31.3

APOLLO EMN14 [53]

DPd vs. Pd

304

Pd ± D 16 mg/kg IV or 1,8 g SC QW (8 w), BIW (16 w), Q4W thereafter; 28-days cycle/s

16.9

>1

12.4 vs. 6.9

HR 0.63

69 vs. 46

25 vs. 4

NM

50 vs. 39

NP, 68 vs. 51

PN, 15 vs. 8

TOURMALINE-MM1 [15]

IRd vs. Rd

722

I, 4mg PO, days 1, 8 and 15, each 28-days cycle.

15

2 (1-3)

20.6 vs. 14.7

HR 0.74

78.3 vs. 71.5

12 vs. 7

NR

74 vs. 69

NCT03143049

PCd vs. Pd

120

Pd ± Cy 400mg days 1, 8, 15 and 22 each 28-days cycle.

NM

>1

NM

NM

NM

NM

NM

OPTIMISMM [31]

PVd vs. Vd

559

P, 4mg days 1-14 (each 21-days) +/- V, SC 1.3mg/m2 days 1, 4, 8, and 11 (cycles 1-8) and days 1 and 8 (>cycle 9); 21-days cycle/s.

15.9

>1

11.2 vs. 7.1

HR 0.61

82.2 vs. 50

OR 5.02

12.5 vs. 3.2

NR

57 vs. 42

CASTOR [54]

DVd vs. Vd

498

D, 16mg/kg IV QW, days 1, 8 and 15 of cycles 1-3; Q3W on day 1 of cycles 4-8, and Q4W thereafter

40

2 (1-10)

16.7 vs. 7.1 HR 0.31

(1 prior line, 27.0 vs. 7.9

HR 0.22)

85 vs. 63

30 vs. 10

NR

TP, 46 vs. 33

PN, 10 vs. 10

Inf, 29 vs. 19

Disc, 10 vs. 9

POLLUX [12]

DRd vs. Rd

569

D, 16mg/kg IV QW days 1, 8, 15 and 22 of cycles 1-2, 8 w and days 1 and 15 of cycles 3 – 6, 16 w and Q4W thereafter; 28-days cycle/s.

44

1 (1-11)

44.5 vs. 17.5

HR 0.44

(1 prior line,

NR vs. 19.6

HR 0.42)

93 vs. 72

57 vs. 23

(MRD,

30.4 vs. 5.3)

NR

NP, 54.1 vs. 39.9

PN, 12 vs. 8.5

NP(F), 6.0 vs. 2.8

ELOQUENT-2 [14]

EloRd vs. Rd

646

Elo 10mg/kg IV, days 1, 8, 15 and 22 of cycles 1-2 and then on days 1 and 15 >cycle 3; 28-days cycle/s.

48

2 (1-4)

19.4 vs. 14.9

HR 0.71

(At 4 y,

21 vs. 14;

H-risk, 15 vs. 7)

79 vs. 66

11 vs. 11

48 vs. 40

Inf, 33 vs. 26

LP, 79 vs. 49

NP, 36 vs. 45

ELOQUENT-3 [55]

EloPd vs Pd

117

Elo 10mg/kg days 1, 8, 15, and 22, cycles 1-2 and 20mg/kg on day 1 of each cycle thereafter; 28-days cycle/s.

9

3 (2-8)

10.3 vs. 4.7

HR 0.54

53 vs. 26

8 vs. 2

HR 0.62

NP, 13 vs. 27

Inf, 13 vs. 22

KEYNOTE-183 [56]

PembroPd vs. Pd

249

Pembro IV 200mg, Q3W; 28-days cycle/s.

8c

4 (2-4)

5.6 vs. 8.4

34 vs. 40

NM

At 6 m,

82 vs. 90

NP, 34 vs. 22

An, 17 vs. 13

PN, 14 vs. 13

AEDTH, 11 vs. 2

  1. aPrimary end point; b Underestimation due to interference with protein studies; c Premature study termination
  2. AE/AEDTH adverse events/adverse events leading to death; AH arterial hypertension; An anemia: BIW twice a week; CF cardiac failure; CR complete response; Cy cyclophosphamide; D daratumumab; d dexamethasone; Disc discontinuation; DKd daratumumab/carfilzomib/dexamethasone; DPd daratumumab/pomalidomide/dexamethasone; DRd daratumumab/lenalidomide/dexamethasone; DVd daratumumab/bortezomib/dexamethasone; Elo elotuzumab; EloPd elotuzumab/pomalidomide/dexamethasone; EloRd elotuzumab/lenalidomide/dexamethasone; G3 grade 3; HR hazard ratio; H-risk high risk; I ixazomib; Inf infection; IRd ixazomib/lenalidomide/dexamethasone; Isa isatuximab; IsaKd isatuximab/carfilzomib/dexamethasone; IsaPd isatuximab/pomalidomide/dexamethasone; IV intravenous; K carfilzomib; Kd carfilzomib/dexamethasone; KRd carfilzomib/lenalidomide/dexamethasone; LP lymphocytopenia; MRD minimal residual disease; NM not mature; NP neutropenia; NP(F) febrile neutropenia; NR not reached; OR odds ratio; ORR overall response rate; OS overall survival; m months; P pomalidomide; PCd pomalidomide/cyclophosphamide/dexamethasone; Pd pomalidomide/dexamethasone; Pembro pembrolizumab; PembroPd pembrolizumab/pomalidomide/dexamethasone; PFS progression-free survival; PN pneumonia; PO per orally; Pts patients; PVd pomalidomide/bortezomib/dexamethasone; QW once weekly; Q2W once every two weeks; Q3W once every three weeks; Q4W once every four weeks; Rd lenalidomide/dexamethasone; TP thrombocytopenia; Vd bortezomib/dexamethasone; w week; y years