Table 3 Safety summary across GPRC5D-targeting agents.

From: GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review

 

Talquetamab

Forimtamigb

MCARH109c (N = 17)

OriCAR-017d (N = 10)

BMS-986393e (N = 33)

0.4 mg/kg SC QWa (n = 143)

0.8 mg/kg SC Q2W (n = 145)

IV cohort (n = 51)

SC cohort (n = 57)

AEs of interest, n (%)

Any grade

Grade 3/4

Any grade

Grade 3/4

Any grade

Grade ≥3

Any grade

Grade ≥3

Any grade

Grade 3/4

Any grade

Grade 3/4

Any grade

Grade 3/4

Anemia

64 (45)

45 (32)

57 (39)

36 (25)

17 (33)

8 (16)

28 (49)

22 (39)

15 (88)

7 (41)

8 (80)

7 (70)

12 (36)

7 (21)

Neutropenia

49 (34)

44 (31)

41 (28)

32 (22)

12 (24)

6 (12)

10 (18)

9 (16)

17 (100)

17 (100)

10 (100)

10 (100)

22 (67)

20 (61)

Lymphopenia

40 (28)

37 (26)

38 (26)

37 (26)

N/R

N/R

N/R

N/R

17 (100)

17 (100)

3 (30)

2 (20)

N/R

N/R

Thrombocytopenia

39 (27)

29 (20)

39 (27)

24 (17)

16 (31)

7 (14)

15 (26)

11 (19)

15 (88)

11 (65)

9 (90)

9 (90)

13 (39)

7 (21)

CRS

113 (79)

3 (2)

105 (72)

1 (1)

42 (82)

1 (2)

45 (79)

1 (2)

15 (88)

1 (6)

10 (100)

0

21 (64)

2 (6)

ICANSf

13 (11)

2 (2)

11 (10)

2 (2)

5 (10)

1 (2)

7 (12)

2 (4)

1 (6)

1 (6)

0

0

2 (6)

0

Skin-related AEsg,h,i,j,k

80 (56)

0

98 (68)

1 (1)

40 (78)

6 (12)

49 (86)

13 (23)

1 (6)

0

3 (30)

0

10 (30)

0

Hair and nail changes

N/R

N/R

N/R

N/R

12 (24)

0

16 (28)

0

N/R

N/R

N/R

N/R

N/R

N/R

Nail-related AEsl,m,n

74 (52)

0

63 (43)

0

N/R

N/R

N/R

N/R

11 (65)

0

3 (30)

0

3 (9)

0

Dysgeusiao

69 (48)

N/A

67 (46)

N/A

N/R

N/R

N/R

N/R

2 (12)

N/A

N/R

N/R

5 (15)

N/A

Dysphagia

34 (24)

0

33 (23)

3 (2)

N/R

N/R

N/R

N/R

N/R

N/R

N/R

N/R

1 (3)

0

Dry mouth

36 (25)

0

53 (37)

0

N/R

N/R

N/R

N/R

1 (6)

0 (0)

N/R

N/R

N/R

N/R

Mucosal toxicityp

N/R

N/R

N/R

N/R

37 (73)

0

44 (77)

3 (5)

N/R

N/R

N/R

N/R

N/R

N/R

Rash-related AEsq

56 (39)

2 (1)

39 (27)

8 (6)

N/R

N/R

N/R

N/R

3 (18)

0

N/R

N/R

N/R

N/R

Infections

82 (57)

24 (17)

73 (50)

17 (12)

31 (61)

11 (22)

26 (46)

15 (26)

3 (18)

2 (12)

N/R

N/R

N/R

N/R

  1. Data cut-off: May 16, 2022 (talquetamab); October 21, 2022 (forimtamig); June 30, 2022 (OriCAR-017); patients were enrolled between September 15, 2020, and June 16, 2021 (MCARH109); September 7, 2022 (BMS-986393).
  2. AE adverse event, CAR-T chimeric antigen receptor T cell, CRS cytokine release syndrome, GI gastrointestinal, GPRC5D G protein–coupled receptor family C group 5 member D, ICANS immune effector cell–associated neurotoxicity syndrome, IV intravenous, N/A not applicable, N/R not reported, Q2W every other week, QW weekly, RP2D recommended phase 2 dose, SC subcutaneous.
  3. aIn phase 1, 0.405 mg/kg SC QW was one of the two RP2Ds; 0.4 mg/kg SC QW was selected as final dosing concentration in phase 2 for operational convenience.
  4. bData presented are for all IV and SC doses combined.
  5. cThree patients received 25 × 106 CAR-T cells and 50 × 106 CAR-T cells, six patients received 150 × 106 CAR-T cells, and five patients received 450 × 106 CAR-T cells.
  6. dThree patients each received 1 × 106 CAR-T cells per kg, 3 × 106 CAR-T cells per kg, and 6 × 106 CAR-T cells per kg, respectively, in the dose-escalation phase. In the dose-expansion phase, one additional patient received the RP2D of 3 × 106 CAR-T cells per kg.
  7. eThirty-three patients received doses of BMS-986393 at 25 (n = 6), 75 (n = 9), 150 (n = 11), 300 (n = 6), and 450 (n = 1) × 106 CAR-T cells.
  8. fIn the ICANS analysis, 122 and 109 patients received talquetamab QW and Q2W, respectively.
  9. gIncludes skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome with talquetamab treatment.
  10. hIncludes rash, skin exfoliation erythema, skin toxicity, dermatitis, dermatitis exfoliative, toxic skin eruption, eczema, erythematous rash, macular rash, and maculopapular rash with forimtamig treatment.
  11. iIncludes pruritus with MCARH109 treatment.
  12. jIncludes pruritus and dry skin with OriCAR-017 treatment.
  13. kIncludes pruritus, maculopapular rash, pain from skin, erythema, and vesicular rash with BMS-986393 treatment.
  14. lIncludes nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and nail ridging with talquetamab treatment.
  15. mIncludes nail disorder with OriCAR-017 treatment.
  16. nIncludes nail bed disorder, nail discoloration, and nail disorder with BMS-986393 treatment.
  17. oDysgeusia has a maximum severity of grade 2 per Common Terminology Criteria for Adverse Events guidelines.
  18. pIncludes dysgeusia, dry mouth, ageusia, stomatitis, salivary hypersecretion, mucosal inflammation, anosmia, dry lip, lip edema, mucosal dryness, mucosal toxicity, and oral paresthesia with forimtamig treatment.
  19. qIncludes rash, maculopapular rash, erythematous rash, and erythema in patients treated with talquetamab and rash in patients who received MCARH109.
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