ne characteristics are summarized in Table 16.
Table 16: Demographics and Baseline Characteristics in Study 2 (Combination Therapy for Relapsed or Refractory Multiple Myeloma)
ECOG = Eastern Cooperative Oncology Group; FISH = Fluorescence in situ hybridization; ISS = International Staging System; Kd = Kyprolis plus dexamethasone; Vd = bortezomib and dexamethasone
Refractory = disease not achieving a minimal response or better, progressing during therapy, or progressing within 60 days after completion of therapy.
Figure 3: Kaplan-Meier Plot of Progression-Free Survival in Study 2
HR = hazard ratio; Kd = Kyprolis plus dexamethasone; PFS = progression-free survival; Vd = bortezomib and dexamethasone
Other endpoints included OS and overall response rate (ORR). At the time of analysis, OS data were not mature. ORR was 77% for patients in the Kd arm and 63% for patients in the Vd arm (see Table 17).
Table 17: Summary of Key Results in Study 2 (Intent-to-Treat Population)*
CI = confidence interval; CR = complete response; Kd = Kyprolis and dexamethasone; ORR = overall response rate; PFS = progression-free survival; sCR = stringent CR; Vd = bortezomib and dexamethasone; VGPR = very good partial response
Eligible patients had 1-3 prior lines of therapy.
PFS and ORR were determined by an Independent Review Committee.
Based on Kaplan Meier estimates.
Based on a stratified Cox's model.
The P-value was derived using stratified log-rank test.
Exact confidence interval.
The P-value was derived using Cochran Mantel Haenszel test.
Includes one patient in each arm with a confirmed PR which may not have been the best response.
The median DOR in subjects achieving PR or better was 21.3 months (95% CI: 21.3, not estimable) in the Kd arm and 10.4 months (95% CI: 9.3, 13.8) in the Vd arm. The median time to response was 1 month (range < 1 to 8 months) in both arms.
14.3 Monotherapy for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (Study 3, Study 4, and Study 5)
Study 3
Study 3 was a multicenter, open-label, dose escalation, single-arm trial that eva luated the safety of carfilzomib monotherapy as a 30-minute infusion in patients with relapsed or refractory multiple myeloma after 2 or more lines of therapy. Patients were excluded if they had a creatinine clearance < 20 mL/min; ALT ≥ 3 × upper limit of normal (ULN), bilirubin ≥ 1.5 × ULN; New York Heart Association class III or IV congestive heart failure; or other significant cardiac conditions. A total of 24 subjects with multiple myeloma were enrolled at the maximum tolerated dose level of 20/56 mg/m2. Carfilzomib was administered twice-weekly for 3 consecutive weeks (Days 1, 2, 8, 9, 15, and 16) of a 28-day cycle. In Cycle 13 onward, the Day 8 and 9 carfilzomib doses could be omitted. Patients received carfilzomib at a starting dose of 20 mg/m2 on Days 1 and 2 of Cycle 1, which was increased to 56 mg/m2 for all subsequent doses. Dexamethasone 8 mg orally or intravenously was required prior to each carfilzomib dose in Cycle 1 and was optional in subsequent cycles. Treatment was continued until disease progression or unacceptable toxicity.
Efficacy was eva luated by ORR and DOR. ORR by investigator assessment was 50% (95% CI: 29, 71) per IMWG criteria (see Table 18). The median DOR in subjects who achieved a PR or better was 8.0 months (Range: 1.4, 32.5).
Table 18: Response Categories in Study 3 (20/56 mg/m2 Monotherapy Regimen)
sCR = stringent complete respo |
