Patients non-eligible for transplant

Sub-analysis of East Asian patients from the ALCYONE trial

ALCYONE (NCT02195479) is a randomized, open-label, phase III trial of daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) vs bortezomib, melphalan, and prednisone (VMP) alone in patients with newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation (auto-SCT).

The Multiple Myeloma (MM) Hub previously covered the overall survival analysis from the ALCYONE trial that was presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition.1 Here, we present the results of a sub-analysis of East Asian patients.2

Patients and treatment2
  • A total of 91 East Asian patients enrolled in the ALCYONE clinical trial were included in this analysis (for details on the ALCYONE study design, click here):
    • Fifty Japanese patients: 24 in the D-VMP group and 26 in the VMP group
    • Forty-one Korean patients: 23 in the D-VMP group and 18 in the VMP group
  • Patient characteristics:
    • Median age: 71 years (range, 64–93)
    • High cytogenetic risk: D-VMP vs VMP, 9 (20%) patients vs 6 (14%), respectively
    • Median number of cycles received, D-VMP vs VMP, respectively:
      • For Japanese patients: 14 (1–21) vs 9 (1–9)
      • For Korean patients: 13 (1–20) vs 6 (1–9)
    • The clinical cut-off date for this analysis was June 12, 2017
Results2

Efficacy

After a median follow-up of 17.1 and 15.9 months for Japanese and Korean patients, respectively:

  • The median progression-free survival (PFS) in the D-VMP group vs the VMP group, respectively, was:
    • Japanese patients: not reached (NR) vs7 months (HR 0.29; 95% CI, 0.07–1.12)
    • Korean patients: NR vs0 months (HR 0.19; 95% CI, 0.06–0.64)
  • The 18-month PFS rate for D-VMP vs VMP, respectively, was:
    • Japanese patients: 84% (95% CI, 55–95) vs 64% (95% CI, 35–82)
    • Korean patients: 81% (95% CI, 56–92) vs 25% (95% CI, 4–54)
  • The best overall responses and the measurable residual disease (MRD)-negative rates (at a 10−5 sensitivity threshold) are reported in Table 1
  • No patients had progressive disease

Table 1. Overall best responses and MRD-negative rates

 

 

Outcome measure

Japanese

Korean

D-VMP

n = 24

VMP

n = 26

D-VMP

n = 23

VMP

n = 18

ORR, %

sCR

CR

VGPR

PR

95.8

50.0

4.2

25.0

16.7

92.3

19.2

3.8

38.5

30.8

91.3

17.4

26.1

39.1

8.7

61.1

5.6

11.1

22.2

22.2

SD, %

4.2

7.7

4.3

27.8

CR or better, %

54.2

23.1

43.5

16.7

VGPR or better, %

79.2

61.5

82.6

38.9

Median time to best response, months

(range)

8.1

(0.8–15.7)

3.5

(0.8–14.4)

4.8

(0.7–14.4)

3.6

(1.4–13.0)

Median duration of response, months

(95% CI)

NE

19.9

NE

13.9

(14.4–19.9)

(9.6–NE)

MRD-negative rate, %

33

8

17

0

CI, confidence interval; CR, complete response; D-VMP, daratumumab + bortezomib + melphalan + prednisone; MRD, measurable residual disease; NE, not estimable; ORR, overall response rate; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VMP, bortezomib + melphalan + prednisone

Safety

  • The incidence of cytopenias was higher in the Japanese group than in the global ALCYONE safety population (Tables 2, 3)
  • The most common non-hematologic Grade 3/4 treatment-emergent adverse event (TEAE) was pneumonia (given as D-VMP vs VMP):
    • Japanese patients: 8.3% vs 0
    • Korean patients: 17.4% vs 0 

Table 2. Most common (˃20%) hematologic TEAEs

 

 

 

TEAE

ALCYONE safety population

Japanese

Korean

D-VMP

n = 346

VMP

n = 354

D-VMP

n = 24

VMP

n = 26

D-VMP

n = 23

VMP

n = 18

Thrombocytopenia, %

48.8

53.7

75.0

61.5

56.5

50.0

Neutropenia, %

49.7

52.5

62.5

61.5

52.2

38.9

Leukopenia, %

13.3

15.0

70.8

50.0

0

5.6

Lymphopenia, %

10.7

10.2

62.5

38.5

0

0

Anemia, %

28.0

37.6

16.7

26.9

30.4

38.9

D-VMP, daratumumab + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse event; VMP, bortezomib + melphalan + prednisone

Table 3. Most common (˃10%) hematologic Grade 3/4 (TEAEs)

 

 

 

TEAE

ALCYONE safety population

Japanese

Korean

D-VMP

n = 346

VMP

n = 354

D-VMP

n = 24

VMP

n = 26

D-VMP

n = 23

VMP

n = 18

Thrombocytopenia, %

34.4

37.6

58.3

46.2

52.2

44.4

Neutropenia, %

39.9

38.7

58.3

61.5

52.2

38.9

Leukopenia, %

8.1

8.5

62.5

42.3

0

5.6

Lymphopenia, %

7.5

6.2

62.5

30.8

0

0

Anemia, %

15.9

19.8

8.3

23.1

26.1

27.8

D-VMP, daratumumab + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse event; VMP, bortezomib + melphalan + prednisone

Conclusions2
  • The efficacy results reported for East Asian patients are consistent with those from the global population of the ALCYONE study, with improvements in ORR and MRD-negativity rates for D-VMP vs VMP
  • Even though a higher rate of cytopenias was reported in Japanese patients compared to the ALCYONE population, these appear to have been well-managed and no patients discontinued treatment due to cytopenias
  • Although patient sample sizes were small, D-VMP treatment in East Asian patients was efficacious with no new safety signals, and the benefit of D-VMP was consistent with that of the global ALCYONE

 

 

References
  1. Mateos M.V. et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020 Jan 11; 395(10218):132–141. DOI: 10.1016/S0140-6736(19)32956-3
  2. Fujisaki T. et al. Daratumumab plus bortezomib, melphalan, and prednisone in East Asian patients with non-transplant multiple myeloma: subanalysis of the randomized phase 3 ALCYONE trial. Ann Hematol. 2019 Dec; 98(12):2805–2814. DOI: 10.1007/s00277-019-03794-9
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