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 61^st 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

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
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

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

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

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

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

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