ASPIRE Study
A randomized, open-label, active-controlled, multicentre, phase 3 study

  • Primary Endpoint
  • Secondary Endpoints
KYPROLIS (carfilzomib) in combination with Rd significantly improved progression-free survival (PFS) vs Rd in patients with relapsed multiple myeloma1,9
This represented a 45% improvement in PFS or a 31% reduction in the risk of disease progression or death in patients with relapsed multiple myeloma (HR=0.69 [95% CI: 0.57–0.83]; p<0.0001; one-sided)1,9
Kaplan-Meier Curve of Progression-Free Survival (PFS) for KYPROLIS + lenalidomide + dexamethasone/KRd (n=396) and lenalidomide + dexamethasone/Rd (n=396). Proportion surviving without progression from 0 to 100 percent. Months since randomization from 0 to 48 months. In the intention-to-treat population, 431 events (disease progression or death), based on outcomes assessed by the independent review committee, had occurred (207 events in the KRd group [52.3%]; 224 events in the Rd group [56.6%]). Patients in the KRd arm demonstrated improved PFS compared with those in the Rd arm (HR = 0.69 [95% CI: 0.57–0.83], p<0.0001); with 26.3 months in the KRd arm vs. 17.6 months in the Rd arm). Patients at risk for Rd: 396 at Month 0, 287 at Month 6, 206 at Month 12, 151 at Month 18, 117 at Month 24, 72 at Month 30, 18 at Month 36, 1 at Month 42, and 0 at Month 48. Patients at risk for KRd: 396 at Month 0, 332 at Month 6, 279 at Month 12, 222 at Month 18, 179 at Month 24, 112 at Month 30, 24 at Month 36, 1 at Month 42, and 0 at Month 48. Patients received KYPROLIS (carfilzomib) through to cycle 18.

Adapted from the KYPROLIS Product Monograph1 and Stewart et al.9

The PFS benefit was consistently observed in all subgroups including those defined according to number of prior lines of therapy, cytogenic risk and age1,9
Subgroup KRd Rd
1 prior line of therapy10 Median PFS (months) 29.6 17.6
Progression or death events, n/N 91/184 88/157
HR=0.71 [95% CI: 0.53–0.96] p=0.0118; one-sided
≥2 prior lines of Therapy10 Median PFS (months) 25.8 16.7
Progression or death events, n/N 116/212 136/239
HR=0.72 [95% CI: 0.56–0.92] p=0.0046; one-sided
High cytogenetic risk11† Median PFS (months) 23.1 13.9
Progression or death events, n/N 31/48 32/52
HR=0.70 [95% CI: 0.43–1.16] p=0.0829; one-sided
Standard cytogenetic risk11† Median PFS (months) 29.6 19.5
Progression or death events, n/N 68/147 94/170
HR=0.66 [95% CI: 0.48–0.90] p=0.0039; one-sided

Open label trial; pre-planned subgroup analysis; results were not adjusted for multiplicity and should be interpreted descriptively.10,11

KRd improved overall survival (OS) vs Rd1,12
The improvement of OS represented a 21% reduction in the risk of death in patients with relapsed multiple myeloma (HR=0.79 [95% CI: 0.67–0.95]; p=0.0045; one-sided)1,12
Kaplan-Meier Curve of Overall Survival (OS) for KYPROLIS + lenalidomide + dexamethasone/KRd (n=396) and lenalidomide + dexamethasone/Rd (n=396). Proportion surviving from 0 to 100 percent. Months since randomization from 0 to 78 months. The pre-planned OS analysis was performed after 246 deaths in the KRd arm (62.1%) and 267 deaths in the Rd arm (67.4%). A statistically significant advantage in OS was observed in patients in the KRd arm compared to patients in the Rd arm (HR = 0.79 [95% CI: 0.67–0.95; p=0.0045]), with 48.3 months in the KRd arm vs. 40.4 months in the Rd arm. Patients at risk for Rd: 396 at Month 0, 356 at Month 6, 313 at Month 12, 281 at Month 18, 243 at Month 24, 220 at Month 30, 199 at Month 36, 176 at Month 42, 149 at Month 48, 133 at Month 54, 113 at Month 60, 69 at Month 66, 20 at Month 72, and 3 at Month 78. Patients at risk for KRd: 396 at Month 0, 369 at Month 6, 343 at Month 12, 316 at Month 18, 282 at Month 24, 259 at Month 30, 232 at Month 36, 211 at Month 42, 190 at Month 48, 166 at Month 54, 149 at Month 60, 88 at Month 66, 22 at Month 72, and 0 at Month 78. Patients received KYPROLIS through to cycle 18.

Adapted from Siegel et al.12

  • The median OS improved by 7.9 months in patients in the KRd arm compared with those in the Rd arm1
  • The pre-planned OS analysis was performed after 246 deaths in the KRd arm and 267 deaths in the Rd arm1,12
  • The median follow-up was approximately 67.1 months1,12
KRd tripled the rate of ‘complete response or better’ (CR + sCR) vs Rd, 32% vs 9%1,9†
Treatment responses in the intention-to-treat population. Key results of overall response rate (ORR), very good partial response (VGPR) or better and complete response (CR) or better for KYPROLIS + lenalidomide + dexamethasone/KRd (n=396) and lenalidomide + dexamethasone/Rd (n=396). Proportion of patients with response (%) from 0 to 100 percent. ORR in KRd arm: 17% of patients demonstrated a partial response (PR), 38% of patients demonstrated a very good partial response (VGPR), 18% of patients demonstrated a complete response (CR), and 14% of patients demonstrated a stringent complete response. ORR in Rd arm: 26% of patients demonstrated a partial response (PR), 31% of patients demonstrated a very good partial response (VGPR), 5% of patients demonstrated a complete response (CR), and 4% of patients demonstrated a stringent complete response. The proportion of patients achieving an objective response was 87% (95% CI: 83–90) in the KRd group compared with 67% (62–71) in the Rd group (p<0.0001). VGPR or better: 70% in the KRd arm and 40% in the Rd arm (p<0.001). CR or better: 32% in the Rd arm and 9% in the Rd arm (p<0.001).
Median duration of response was:9
  • 28.6 months [95% CI: 24.9–31.3] in the KRd arm, vs
  • 21.2 months [95% CI: 16.7––25.8] in the Rd arm
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STUDY DESIGN
BASELINE
CHARACTERISTICS
Learn about the ASPIRE Study by reading the trial abstract.
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* KYPROLIS treatment was administered for a maximum of 18 cycles unless discontinued early for disease progression or unacceptable toxicity. Lenalidomide and dexamethasone administration could continue until progression or unacceptable toxicity.1

† Percentages have been rounded.

CI, confidence interval; CR, complete response; HR, hazard ratio; KRd, KYPROLIS + lenalidomide + dexamethasone; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; Rd, lenalidomide + dexamethasone; VGPR, very good partial response.

Patient
Baseline characteristics1,9
Characteristics KRd (n=396) Rd (n=396)
Age
Median (years) 64 65
Range (years) 38–87 31–91
Distribution [number of patients (%)]
18–64 years 211 (53) 188 (48)
≥65 years 185 (47) 208 (53)
ECOG Performance Status [number of patients (%)]
0 or 1 356 (90) 361 (91)
2 40 (10) 35 (9)
Cytogenic Risk at Study Entry [number of patients (%)]
High risk 48 (12) 52 (13)
Standard risk 147 (37) 170 (43)
Unknown 201 (51) 174 (44)
Creatinine Clearance*
Median (mL/min) 79 (39–212) 79 (30–208)
Distribution [number of patients (%)]
30 to <50 mL/min 19 (5) 32 (8)
50 to <80 mL/min 185 (47) 170 (43)
≥80 mL/min 192 (49) 194 (49)
Previous therapies in patients participating in the ASPIRE study
ITT Population [number of patients (%)]9
Previous Regimens† KRd (n=396) Rd (n=396)
1 regimen 184 (47) 157 (40)
2 or 3 regimens 211 (53) 238 (60)
Transplant 217 (55) 229 (58)
Bortezomib 261 (66) 260 (66)
Lenalidomide 79 (20) 78 (20)
Study eligibility:9
  • Prior bortezomib was permitted provided patients did not have disease progression during treatment
  • Prior lenalidomide and dexamethasone (Rd) was permitted provided patients did not discontinue therapy due to adverse effects, have disease progression during the first 3 months of treatment, or have progression at any time during treatment if Rd was their most recent treatment

* Patients were required to have a creatinine clearance of ≥50 mL/min at screening; one patient in the Rd group had a creatinine clearance of <30 mL/min at baseline.9

† One patient (0.3%) in each group received 4 prior regimens.9

ITT, intent to treat; KRd, KYPROLIS® + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone.

ASPIRE was a randomized, open-label, active-controlled, phase 3 study with the following study design1
Patients with relapsed multiple myeloma who had received 1 to 3 prior lines of therapy (N=792) were randomized 1:1 to one of two groups: KRd twice weekly* (n=396) which consisted of KYPROLIS® (carfilzomib; 20/27 mg/m2), lenalidomide (25 mg), and dexamethasone (40 mg), or Rd twice weekly* (n=396) consisting of lenalidomide (25 mg) and dexamethasone (40 mg). The primary endpoint was progression-free survival (PFS).

* KYPROLIS (carfilzomib) treatment was administered for a maximum of 18 cycles unless discontinued early for disease progression or unacceptable toxicity. Lenalidomide and dexamethasone administration could continue until progression or unacceptable toxicity.1

† Cycles were repeated until disease progression or unacceptable toxicity.1

PFS was determined by an Independent Review Committee.1

KRd, KYPROLIS + lenalidomide + dexamethasone; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.