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Once- vs. Twice-Weekly Carfilzomib in NDMM
was 47% (95%CI: 33%-68%) and 51% (95%CI: 38%- 70%) in the once-weekly group and in the twice-weekly group, respectively (Figure 3A), with no significant differ- ence in the risk of progression (HR: 1.04; P=0.92) within the two groups when adjusting for age, ISS, FISH, Frailty Score and response to induction. No differences in 3-year PFS-2_m (65% vs. 74%; HR: 0.85; P=0.74) and OS_m (72% vs. 73%; HR: 0.82; P=0.71) were observed between the two groups (Figure 3B and C).
Overall, the proportion of patients achieving a PR or better was 92% in the once-weekly versus 90% in the twice-weekly group (P=0.76), including 22% and 29% of patients obtaining a CR or better (P=0.41). Responses were rapid: median time to PR or better was 1.9 months in the once-weekly group and 1.2 months in the twice- weekly group.
Carfilzomib dose reduction was necessary in 18 (29%) patients receiving the once-weekly schedule and in 17 (30%) patients receiving the twice-weekly schedule. The median relative dose intensity of carfilzomib [once week- ly 97.6% (IQR 88.3-100%); twice weekly 97.2% (IQR 90.4-100%)] was similar in the two groups (P=0.75). Dexamethasone dose reduction was necessary in 13 (21%) patients receiving the once-weekly schedule and in 18 (32%) patients receiving the twice-weekly schedule. The median relative dose intensity of dexamethasone
[once weekly 100% (IQR 82.6-100%); twice weekly 100% (IQR 88.5-100%)] was similar in the two groups (P=0.85). Cyclophosphamide dose reduction was neces- sary in 7 (11%) patients receiving the once-weekly sched- ule and in 15 (27%) patients receiving the twice-weekly schedule. Nevertheless, the median relative dose intensity of cyclophosphamide [once weekly 96.85% (IQR 90.8- 100%); twice weekly 96.75% (IQR 88.6-100%)] was sim- ilar in the two groups (P=0.97). The most common AE leading to carfilzomib dose reduction were acute kidney injury (1 patient in the once-weekly group and 2 patients in the twice-weekly group), infections (2 patients in each group), and hypertension (4 patients in the once-weekly group and none in the twice-weekly group). Treatment- related AE leading to the discontinuation of carfilzomib occurred in 17 (27%) patients in the once-weekly group and 17 (30%) patients in the twice-weekly group. The most common AE leading to carfilzomib discontinuation were cardiac injury (6 patients in the once-weekly group and 6 patients in the twice-weekly group), infections (3 patients in the once-weekly group and 3 patients in the twice-weekly group), and thromboembolism (2 patients in the once-weekly group and 1 in the twice-weekly group). Cardiac events leading to drug discontinuation during induction (3 and 2) and maintenance (3 and 4) occurred at similar rates in patients receiving once- versus
AB
C
Figure 3. Analysis from start of maintenance therapy. (A) Progression-free survival from start of maintenance therapy (PFS_m). (B) Progression-free survival 2 from start of maintenance therapy (PFS-2_m). (C) Overall survival from start of maintenance therapy (OS_m). (Note that PFS-2 was calculated from the date of enrollment to the date of second relapse/progression or death or the date the patient was last known to be in remission.)
haematologica | 2019; 104(8)
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