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Letters to the Editor
ences in CIR (HR: 0.88, 95% CI: 0.65-1.20; P=0.43) or NRM (HR 1.39, 95% CI: 0.61-3.16; P=0.43) between the two groups.
In the matched cohort with ≤PR at ASCT (n=140), there was a trend for improved OS (HR: 0.53, 95% CI: 0.28-1.02; P=0.06) for the Mel200 group, but not in PFS (HR: 1.01, 95% CI: 0.60-1.71; P=0.97), CIR (HR: 0.97, 95% CI: 0.63-1.49; P=0.90), or NRM (HR: 0.84, 95% CI: 0.30-2.37; P=0.74). In patients with ≥VGPR at ASCT (n=164), there were no statistical differences between the two melphalan groups in OS (HR: 0.93, 95% CI: 0.49- 1.75; P=0.82), PFS (HR: 0.82, 95% CI: 0.49-1.36; P=0.43), CIR (HR: 0.81, 95% CI: 0.52-1.27; P=0.36), or NRM (HR: 2.41, 95% CI: 0.60-9.64; P=0.21).
Hematological toxicities were universal as expected and there were no significant differences in either neu- trophil or platelet engraftments between the two groups. Gastrointestinal toxicity of any grade was the most com- monly reported side effect, observed in 91% and 96% of Mel140 and Mel200 patients, respectively (P=0.13). Mucositis rates were significantly higher with Mel200 (49%) compared to Mel140 (29%; P=0.002). The majori- ty were grades 1-2, 26% in the Mel140 group and 48% in the Mel200 group. A higher percentage of patients in the Mel200 group had febrile neutropenia (34% vs. 25%;
P=0.20), but the documented infection rates were com- parable (25% in the Mel200 group vs. 26% in the Mel140 group; P=0.88). Renal toxicity was observed more frequently in the Mel140 group (5% vs. 2%; P=0.11); this was expected because even after matching, higher proportion of patients in this group had renal impairment.
Other non-hematological toxicities were less frequent. Higher rate of cardiac toxicity in the Mel140 group (8% in the Mel140 group vs. 3% in the Mel200 group; P=0.10). The rates of grades 3-4 non-hematological toxi- cities for the 304 matched patients were 33% for Mel140 and 22% for Mel200 (P=0.09). During the study period, 33 of the 76 patients in the Mel140 group and 89 of the 228 patients in the Mel200 group died. The most com- mon cause of death was relapse/recurrent disease (81% for both Mel140 and Mel200; P=1.00). The 1-year NRM was 1% in the Mel140 group, compared to 3% in the Mel200 group (P=0.64).
In this study, we found that a reduced dose of Mel140 is feasible for use in older MM patients and those considered ineligible for Mel200. In patients with VGPR or better at transplant, use of Mel140 had comparable response rates, PFS, and OS to Mel200. In patients with ≤PR at ASCT, there was a trend towards improved OS with Mel200.
Table 2. Patient and disease characteristics by melphalan dose for matched patients. PR or worse
Mel140 (N=35)
5 (14) 30 (86)
22 (63) 13 (37)
6 (17) 12 (34) 17 (49)
23 (70) 10 (30)
20 (87) 3 (13)
22 (63) 13 (37)
14 (40) 21 (60)
21 (60) 14 (40)
Induction treatment
Conventional
IMiD 7(20)
Mel200 (N=105)
20 (19) 85 (81)
69 (66) 36 (34)
35 (33) 33 (31) 37 (35)
77 (75) 25 (25)
68 (92) 6 (8)
80 (76) 25 (24)
27 (26) 78 (74)
71 (68) 34 (32)
3 (3) 12(11) 48 (46) 42 (40)
23 (22)
82 (78)
VGPR or better
P Mel140 Mel200 P
(N=41) (N=123)
0.62 7 (17) 26 (21) 0.66 34 (83) 97 (79)
0.84 25 (61) 71 (58) 0.85 16 (39) 52 (42)
0.16 8 (20) 33 (27) 0.45 19 (46) 44 (36)
14 (34) 46 (37)
0.50 26 (67) 81 (71) 0.69 13 (33) 33 (29)
0.44 27 (87) 80 (89) 0.75 4 (13) 10 (11)
0.13 29 (71) 93 (76) 0.54 12 (29) 30 (24)
0.13 17 (41) 38 (31) 0.25 24 (59) 85 (69)
0.42 20 (49) 87 (71) 0.014 21 (51) 36 (29)
0.43 0 2 (2) 0.40 1(2) 7(6)
Measure, n (%)
Age at ASCT < 65 years ≥ 65 years
Sex Male
Female
ISS stage I
II III
Cytogenetic risk Standard
High
LDH Normal High
Creatinine < 2 mg/dL ≥ 2 mg/dL
Karnofsky performance status <90
≥90
HCT-CI ≤3 >3
PI
IMiD + PI
Maintenance therapy No
Yes
17 (49) 10 (29)
6 (17) 29 (83)
20 (49) 20 (49)
0.64 11 (27) 30 (73)
42 (34) 72(59)
37 (30) 0.84
86 (70)
1 (3)
ASCT: autologous stem cell transplantation; HCT-CI: hematopoietic cell transplantation-specific comorbidity index; IMiD: immunomodulatory imide drug; ISS: International Staging System; LDH: lactate dehydrogenase; Mel: melphalan; PR: partial response; PI: proteasome inhibitor; VGPR: very good partial response.
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