Page 219 - Haematologica Vol. 109 - July 2024

ARTICLE - Carfilzomib, thalidomide and dexamethasone (KTd) in RRMM S. Ninkovic et al.
ued treatment during the induction phase (most commonly due to progressive disease [n=16; 18%]; unacceptable ad- verse events [n=7; 8%] and patients’ decision [n=7; 8%]) while 11 patients (12%) discontinued treatment during the maintenance phase (most commonly due to progressive disease [n=6; 7%], unacceptable adverse events [n=4, 4%] or unresolved adverse events [n=1; 1%]). Thirty-nine patients (43%) completed the pre-defined 18 cycles of therapy. The relative dose intensity (RDI), defined as the proportion of the intended carfilzomib dose, decreased significantly with increasing dose levels (the median RDI was 98.8% for the 20/27 mg/m2 dose [n=21] vs. 93.3% for the 20/36 mg/m2 dose [n=6] and 89.9% for the 20/56 mg/m2 dose [n=60]; P<0.001) although there was no difference in the
median RDI observed between the non-Asian and Asian cohorts of patients (91.5% vs. 95.6%; P=0.17). Almost all patients (99%) experienced at least one adverse event; 74% of patients experienced at least one event attributed to carfilzomib, 66% experienced at least one event related to dexamethasone while 76% of patients reported events related to thalidomide. Carfilzomib-related adverse events triggered a dose delay for 42% of patients, dose delay and reduction for 13% and carfilzomib discontinuation in 17% of patients. Thalidomide was discontinued due to adverse events in 21% of patients.
The most common adverse events of any grade are sum- marized in Table 3 and include dyspnea (38.9%), upper respiratory tract infection (36.7%), peripheral sensory neu-
Table 1. Patients’ demographics and disease characteristics at baseline.
Characteristic
Not Asian N=46
Asian N=44
Total N=90
Age in years Median Range
68.8 41.9-84.5
64.4 42.6-77.1
66.3 41.9-84.5
Age distribution, N of patients (%) 18-64 years old
65-74 years old
≥75 years old
15 (33) 19 (41) 12 (26)
24 (55) 19 (43) 1 (2)
39 (43) 38 (42) 13 (14)
Sex, N of patients (%) Female
Male
19 (41) 27 (59)
17 (39) 27 (61)
36 (40) 54 (60)
Race, N of patients (%) Caucasian
East Asian South-East Asian
46 (100) 0 (0)
0 (0)
0 (0) 24 (55) 20 (45)
46 (51) 24 (27) 20 (22)
Geographic region, N of patients (%) ANZ
Asia
46 (100) 0 (0)
3 (7) 41(93)
49 (54) 41 (46)
ECOG PS, N of patients (%) 012Missing
32 (70) 9 (20) 5 (11) 0 (0)
21 (48) 12 (27) 4 (9) 7 (16)
53 (59) 21 (23) 9 (10) 7 (8)
CrCl distribution, N of patients (%) <30 mL/min
30-60 mL/min
≥60 mL/min
Unknown
3 (7) 8 (17) 35 (76) 0 (0)
1 (2) 9 (20) 28 (64) 6 (14)
4 (4) 17 (19) 63 (70) 6 (7)
Serum ß2-microglobulin, N of patients (%)
≤3.5 mg/L
>3.5 to ≤5.5 mg/L >5.5 mg/L Unknown
23 (50) 12 (26) 10 (22) 1 (2)
34 (77) 2 (5) 4 (9) 4 (9)
57 (63) 14 (16) 14 (16) 5 (6)
Serum albumin, N of patients (%) <35 g/L
≥35 g/L
Unknown
21 (46) 24 (52) 1 (2)
13 (30) 31 (70) 0 (0)
34 (38) 55 (61) 1 (1)
Characteristic
Not Asian N=46
Asian N=44
Total N=90
Serum LDH, N of patients (%) Normal, <ULN
High, >ULN
31 (67) 15 (33)
9 (20) 35 (80)
40 (44) 50 (56)
R-ISS stage, N of patients (%)
II
III Unknown
6 (13) 2 (4) 26 (57) 12 (26)
4 (9) 7 (16) 21 (48) 12 (27)
10 (11) 9 (10) 47 (52) 24 (27)
Time since diagnosis in years Median
Range
4.5 0.3-15.8
3.5 0.3-15.5
3.5 0.3-15.8
Prior lines of therapy Median
Range
1.5 1-3
1 1-3
1 1-3
Distribution of prior therapy, N of patients (%)
1 prior line 2 prior lines 3 prior lines
23 (50) 11 (24) 12 (26)
25 (57) 9 (20) 10 (23)
48 (53) 20 (22) 22 (24)
Previous therapies, N of patients (%) Bortezomib
Thalidomide
Lenalidomide
Pomalidomide AutoSCT
28 (61) 7 (15) 5 (11) 1 (2) 13 (28)
24 (55) 22 (50) 5 (11) 0 (0)
52 (58) 29 (32) 10 (11) 1 (1)
18 (41)
31 (34)
Prior peripheral neuropathy, N of patients (%)
Yes Missing
11 (24) 4 (9)
7 (16) 3 (7)
18 (20) 7 (8)
Left ventricular ejection fraction (%) Median
Range
N=45 60.0 44.0-80.0
N=29 63.0 55.0-74.0
N=74 61.5 44.0-80.0
ANZ: Australia and New Zealand; ECOG PS: Eastern Cooperative On- cology Group performance status; CrCl: creatinine clearance; LDH: lactate dehydrogenase; ULN: upper limit of normal; R-ISS: Revised International Staging System; AutoSCT: autologous stem cell trans- plant.
Haematologica | 109 July 2024
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