- KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. ... Read More
KRd vs Rd study results
Median PFS
PFS at 18 months
PFS by 1 previous line
PFS by 2 or 3 previous lines
PFS in frail-subgroup patients
Superior median progression-free survival: 26.3 months for KRd vs 17.6 months with Rd1
Adding KYPROLIS® to Rd significantly increased median PFS survival by 8.7 months1
Primary endpoint: progression-free survival1
Median PFS
KRd = 26.3 months
Rd = 17.6 months
HR = 0.69 (95% CI: 0.57-0.83);
P = 0.0001, two-sided
NCCN Guidelines®: Carfilzomib (KYPROLIS®) in combination with lenalidomide and dexamethasone (KRd) is a preferred regimen for relapsed multiple myeloma2
Carfilzomib (KYPROLIS®) in combination with lenalidomide and dexamethasone (KRd) has a category 1 designation in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma (Version 3.2020) for previously treated multiple myeloma.2
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their applications or use in any way.
KRd = KYPROLIS®+lenalidomide and dexamethasone; Rd = lenalidomide+dexamethasone; PFS = progression-free survival; HR = hazard ratio; CI = confidence interval; NCCN = National Comprehensive Cancer Network.
Post hoc analysis: progression-free survival at 18 months was 64.5% with KRd vs 46.6% with Rd alone1,3
Progression-free survival at 18 months1,3
Post hoc analysis: demonstration of progression-free survival at 18 months was not a study objective.
KRd = KYPROLIS® (carfilzomib), lenalidomide, and dexamethasone; PFS = progression-free survival; Rd = lenalidomide and dexamethasone.
Post hoc analysis: at first relapse, KRd demonstrated a 12-month increase in median progression-free survival over Rd alone4
1 previous line of therapy4
Post hoc analysis: demonstration of progression-free survival efficacy within these subgroups was not a study objective. The study was not powered to evaluate progression-free survival efficacy within each of these subgroups.
KRd = KYPROLIS® (carfilzomib), lenalidomide, and dexamethasone; PFS = progression-free survival; Rd = lenalidomide and dexamethasone.
Post hoc analysis: KRd demonstrated a 9.1-month increase in median progression-free survival over Rd alone in patients who had received 2 or 3 previous lines of therapy4
2 or 3 previous lines of therapy4
Post hoc analysis: demonstration of progression-free survival within these subgroups was not a study objective. The study was not powered to evaluate progression-free survival efficacy within each of these subgroups.
KRd = KYPROLIS® (carfilzomib), lenalidomide, and dexamethasone; PFS = progression-free survival; Rd = lenalidomide and dexamethasone.
Post-hoc analysis: Frail-subgroup patients with KRd experienced mPFS 24.1 months vs 15.9 months with Rd alone12,*,†
Patients’ age, ECOG PS, and medical history (comorbidities) were used to evaluate frailty status12,*
Median PFS
KRd significantly increased median overall survival by 7.9 months vs Rd alone (48.3 months KRd vs 40.4 months Rd alone)1
KRd reduced the risk of death by 21% compared to Rd alone1
Secondary endpoint: overall survival1
HR (KRd/Rd) = 0.79 (95% CI: 0.67-0.95);
P = 0.0091, two-sided.
KRd = KYPROLIS®+lenalidomide and dexamethasone; Rd = lenalidomide+dexamethasone; OS = overall survival; HR = hazard ratio; CI = confidence interval.
Response by category
≥ CR over time
≥ CR at 1st relapse
Adding KYPROLIS® to Rd tripled the patient’s chance of achieving a complete response or better (KRd vs Rd)1
Secondary endpoint: responses by category1
ORR (≥ PR)
KRd = 87% (95% CI: 0.83-0.90)
Rd = 67% (95% CI: 0.62-0.71)
P < 0.0001, two-sided
IMWG uniform response criteria5
| Response | Multiple myeloma response criteria |
|---|---|
| Stringent complete response (sCR) | CR as defined below plus normal free light chain (FLC) ratio* and absence of clonal cells in bone marrow biopsy by immunohistochemistry† |
| Complete response (CR) | Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates |
| Very good partial response (VGPR) | Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 hours |
| Partial response (PR) |
≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 hours If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥ 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥ 30%. In addition to these criteria, if present at baseline, a ≥ 50% reduction in the size (SPD)‡ of soft tissue plasmacytomas is also required |
Post hoc analysis: adding KYPROLIS® to Rd led to an increase in the rate of ≥ CR6
In a post hoc analysis of CR over time, ≥ CR rates were higher for KRd vs Rd across all time points, reaching 31.9% (KRd) vs 9.3% (Rd) at 30 months after the start of treatment6
Cumulative rates of ≥ CR6
- At 9 months, 20.9% of KRd-treated patients attained ≥ CR vs 4.9% of patients treated with Rd alone6
- Median time from treatment start to ≥ CR was 6.7 months for KRd patients and 8.3 months for Rd patients6
- The percentage of KRd-treated patients achieving ≥ CR increased with each cycle6
- Post hoc analysis: demonstration of CR over time was not a study objective. The study was not powered to assess CR over time in this subgroup
≥ CR = complete response or better; KRd = KYPROLIS® (carfilzomib), lenalidomide, and dexamethasone; Rd = lenalidomide+dexamethasone.
Post hoc analysis: complete response rates at first relapse (KRd vs Rd study)4
≥ CR at first relapse4
Addition of KYPROLIS® to Rd improves PFS and OS while maintaining health-related quality of life for patients with RMM1,7
- KRd showed superior median PFS (26.3 months with KRd vs 17.6 months with Rd; HR = 0.69; 95% CI: 0.57-0.83; P = 0.0001 two-sided)1
- KRd demonstrated superior median OS (48.3 months with KRd vs 40.4 months with Rd; HR = 0.79; 95% CI: 0.67-0.95; P = 0.0091 two-sided)1
- Survival was improved while maintaining HRQOL1,7
GHS/QOL scores and mean treatment differences7
Stewart AK, et al. J Clin Oncol. 2016;34:3921-3930. Reproduced with permission.
© 2018 American Society of Clinical Oncology. All rights reserved.
- The QLQ-C30 contains an overall GHS/QOL domain, five functional domains (physical, emotional, cognitive, social, and role functioning), and nine symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties)7
- Evidence for development and psychometric quality of the scale is available across a large body of peer-reviewed published literature8-10
- Validity of the QLQ-C30 has been demonstrated for patients with multiple myeloma8-10
- Compliance was calculated using the proportion of randomly assigned patients (intent-to-treat population) and the proportion of patients expected to have an assessment (alive and on study treatment)7
- Logistic regression models were used to explore relationships between the probability of missing data and baseline scores (baseline models) and between the probability of missing data and previous scores (previous value models)7
- Comparisons between treatment groups were analyzed using a restricted maximum likelihood-based mixed model for repeated measures (MMRM) under the assumption of missing data at random7
- GHS/QOL was assessed against an overall one-sided significance level of P = 0.025 (two-sided significance level of P = 0.05) under fixed sequence hierarchical testing procedure to adjust for multiplicity7
- At the time of analysis, the reported P values were considered descriptive and unadjusted for multiplicity, because OS data were not mature at that point, so the GHS/QOL endpoint was not to be tested. Since this analysis, superiority of KRd OS over Rd has been established
- Open-label design—patients were aware of their treatment allocation before completing their baseline assessment7
- Differential attrition across groups7
- GHS/QOL scores account for only 1 aspect of HRQOL. The GHS/QOL domain alone is not adequate to fully assess the broad and multidimensional concept of HRQOL
- Least mean scores were adjusted for baseline score, baseline score by visit interaction, and random assignment stratification factors (baseline ß2-microglobulin levels, prior bortezomib, and prior lenalidomide)7
- A minimally important difference (MID) represents the smallest group-level difference in a PRO score considered clinically meaningful, and an MID of 5 points for between-group differences on the QLQ-C30 GHS/QOL was prespecified7
- An MID of 5 points is not universally agreed upon as the value for indicating a clinically meaningful change11
- Only GHS/QOL scores exhibited statistical significance from the QLQ-C307
- GHS/QOL reached the MID of 5 points only at cycle 127
Meet Elizabeth, a 66-year-old African American female
Hypothetical KRd case study of a standard-risk* patient with multiple myeloma at first relapse
Time for a deep and durable response
- Retired nurse with active, healthy lifestyle
- Hypertension well controlled with medication
- M-protein levels monitored regularly
- Standard-risk cytogenetics*
- ECOG PS 1
Not an actual patient
Dr. Berenson expert video
When multiple myeloma relapses, see why Dr. James Berenson chooses KRd for his patients
See KRd dosing