User login
Adding carfilzomib (K) to treatment with lenalidomide and dexamethasone (Rd) can improve overall survival (OS) in patients with relapsed or refractory multiple myeloma (MM), according to research published in the Journal of Clinical Oncology.
Final results from the phase 3 ASPIRE trial showed that KRd reduced the risk of death by 21% and extended OS by 7.9 months, when compared to Rd.
In patients at first relapse, KRd was associated with an OS improvement of 11.4 months.
“Results from the final analysis of the phase 3 ASPIRE trial . . . are significant, as they further validate carfilzomib, lenalidomide, and dexamethasone as a standard-of-care regimen for patients with relapsed or refractory multiple myeloma,” said study author Keith Stewart, MBChB, of Mayo Clinic in Scottsdale, Arizona.
“Furthermore, these data showed that early use of carfilzomib, lenalidomide, and dexamethasone at first relapse provided nearly 1 additional year of survival for patients, regardless of prior treatment with bortezomib or transplant.”
ASPIRE enrolled 792 MM patients who had received a median of 2 prior therapies (range, 1-3). They were randomized to receive KRd (n=396) or Rd (n=396). Baseline characteristics were well balanced between the treatment arms.
Details on patients and treatment, as well as interim results from ASPIRE, were reported at the 2014 ASH Annual Meeting and published in NEJM in January 2015.
Treatment update
In the final analysis, there were 340 patients in the KRd arm and 358 in the Rd arm who stopped study treatment.
Reasons for discontinuation (in the KRd and Rd arms, respectively) were disease progression (n=188 and 224), adverse events (AEs, n=79 and 85), other reasons (n=61 and 35), withdrawn consent (n=10 and 12), and noncompliance (n=2 and 1).
A total of 182 patients in the KRd arm and 211 in the Rd arm received subsequent treatment for MM. These treatments were generally balanced between the KRd and Rd arms.
The median time to next treatment from the time of randomization was 39.0 months in the KRd arm and 24.4 months in the Rd arm (hazard ratio [HR]=0.65 P<0.001).
Survival
Interim ASPIRE data had shown a significant improvement in progression-free survival (PFS) and a trend toward improved OS in patients who received KRd. Now, researchers have observed a significant improvement in both endpoints with KRd.
The data cutoff for the final analysis was April 28, 2017. For PFS, the median follow-up was 48.8 months in the KRd arm and 48.0 months in the Rd arm.
The median PFS was 26.1 months in the KRd arm and 16.6 months in the Rd arm (9.5-month improvement, HR=0.66; P<0.001). The 3-year PFS rates were 38.2% and 28.4%, respectively. And the 5-year PFS rates were 25.6% and 17.3%, respectively.
The median follow-up for OS was 67.1 months. The median OS was 48.3 months in the KRd arm and 40.4 months in the Rd arm (7.9-month improvement, HR=0.79, P=0.0045).
The researchers also performed subgroup analyses according to prior lines of therapy, prior bortezomib exposure at first relapse, and prior transplant at first relapse.
In patients who had received 1 prior line of therapy, the median OS was 47.3 months in the KRd arm and 35.9 months in the Rd arm (11.4-month improvement, HR=0.81). For patients with 2 or more prior lines of therapy, the median OS was 48.8 months and 42.3 months, respectively (6.5-month improvement, HR=0.79).
Among patients with prior bortezomib exposure at first relapse, the median OS was 45.9 months in the KRd arm and 33.9 months in the Rd arm (12-month improvement, HR=0.82). Among patients without prior bortezomib exposure at first relapse, the median OS was 48.3 months and 40.4 months, respectively (7.9-month improvement, HR=0.80).
Among patients with prior transplant at first relapse, the median OS was 57.2 months in the KRd arm and 38.6 months in the Rd arm (18.6-month improvement, HR=0.71).
Safety
The incidence of treatment-emergent AEs was 98% in the KRd arm and 97.9% in the Rd arm. The incidence of grade 3 or higher AEs was 87% and 83.3%, respectively. The incidence of serious AEs was 65.3% and 56.8%, respectively.
Treatment discontinuation due to an AE occurred in 19.9% of patients in the KRd arm and 21.5% of patients in the Rd arm.
AEs of interest (in the KRd and Rd arms, respectively) included acute renal failure (9.2% and 7.7%), cardiac failure (7.1% and 4.1%), ischemic heart disease (6.9% and 4.6%), hypertension (17.1% and 8.7%), hematopoietic thrombocytopenia (32.7% and 26.2%), and peripheral neuropathy (18.9% and 17.2%).
Fatal AEs were reported in 11.5% of patients in the KRd arm and 10.8% of those in the Rd arm.
Fatal AEs reported in at least 2 patients in the KRd arm included (in the KRd and Rd arms, respectively) cardiac disorders (2.6% and 2.3%), pneumonia (1.5% and 0.8%), sepsis (0.8% for both), myocardial infarction (0.8% and 0.5%), acute respiratory distress syndrome (0.8% and 0%), death (0.5% for both), and cardiac arrest (0.5% and 0.3%).
This trial was funded by Onyx Pharmaceuticals, Inc. 
Adding carfilzomib (K) to treatment with lenalidomide and dexamethasone (Rd) can improve overall survival (OS) in patients with relapsed or refractory multiple myeloma (MM), according to research published in the Journal of Clinical Oncology.
Final results from the phase 3 ASPIRE trial showed that KRd reduced the risk of death by 21% and extended OS by 7.9 months, when compared to Rd.
In patients at first relapse, KRd was associated with an OS improvement of 11.4 months.
“Results from the final analysis of the phase 3 ASPIRE trial . . . are significant, as they further validate carfilzomib, lenalidomide, and dexamethasone as a standard-of-care regimen for patients with relapsed or refractory multiple myeloma,” said study author Keith Stewart, MBChB, of Mayo Clinic in Scottsdale, Arizona.
“Furthermore, these data showed that early use of carfilzomib, lenalidomide, and dexamethasone at first relapse provided nearly 1 additional year of survival for patients, regardless of prior treatment with bortezomib or transplant.”
ASPIRE enrolled 792 MM patients who had received a median of 2 prior therapies (range, 1-3). They were randomized to receive KRd (n=396) or Rd (n=396). Baseline characteristics were well balanced between the treatment arms.
Details on patients and treatment, as well as interim results from ASPIRE, were reported at the 2014 ASH Annual Meeting and published in NEJM in January 2015.
Treatment update
In the final analysis, there were 340 patients in the KRd arm and 358 in the Rd arm who stopped study treatment.
Reasons for discontinuation (in the KRd and Rd arms, respectively) were disease progression (n=188 and 224), adverse events (AEs, n=79 and 85), other reasons (n=61 and 35), withdrawn consent (n=10 and 12), and noncompliance (n=2 and 1).
A total of 182 patients in the KRd arm and 211 in the Rd arm received subsequent treatment for MM. These treatments were generally balanced between the KRd and Rd arms.
The median time to next treatment from the time of randomization was 39.0 months in the KRd arm and 24.4 months in the Rd arm (hazard ratio [HR]=0.65 P<0.001).
Survival
Interim ASPIRE data had shown a significant improvement in progression-free survival (PFS) and a trend toward improved OS in patients who received KRd. Now, researchers have observed a significant improvement in both endpoints with KRd.
The data cutoff for the final analysis was April 28, 2017. For PFS, the median follow-up was 48.8 months in the KRd arm and 48.0 months in the Rd arm.
The median PFS was 26.1 months in the KRd arm and 16.6 months in the Rd arm (9.5-month improvement, HR=0.66; P<0.001). The 3-year PFS rates were 38.2% and 28.4%, respectively. And the 5-year PFS rates were 25.6% and 17.3%, respectively.
The median follow-up for OS was 67.1 months. The median OS was 48.3 months in the KRd arm and 40.4 months in the Rd arm (7.9-month improvement, HR=0.79, P=0.0045).
The researchers also performed subgroup analyses according to prior lines of therapy, prior bortezomib exposure at first relapse, and prior transplant at first relapse.
In patients who had received 1 prior line of therapy, the median OS was 47.3 months in the KRd arm and 35.9 months in the Rd arm (11.4-month improvement, HR=0.81). For patients with 2 or more prior lines of therapy, the median OS was 48.8 months and 42.3 months, respectively (6.5-month improvement, HR=0.79).
Among patients with prior bortezomib exposure at first relapse, the median OS was 45.9 months in the KRd arm and 33.9 months in the Rd arm (12-month improvement, HR=0.82). Among patients without prior bortezomib exposure at first relapse, the median OS was 48.3 months and 40.4 months, respectively (7.9-month improvement, HR=0.80).
Among patients with prior transplant at first relapse, the median OS was 57.2 months in the KRd arm and 38.6 months in the Rd arm (18.6-month improvement, HR=0.71).
Safety
The incidence of treatment-emergent AEs was 98% in the KRd arm and 97.9% in the Rd arm. The incidence of grade 3 or higher AEs was 87% and 83.3%, respectively. The incidence of serious AEs was 65.3% and 56.8%, respectively.
Treatment discontinuation due to an AE occurred in 19.9% of patients in the KRd arm and 21.5% of patients in the Rd arm.
AEs of interest (in the KRd and Rd arms, respectively) included acute renal failure (9.2% and 7.7%), cardiac failure (7.1% and 4.1%), ischemic heart disease (6.9% and 4.6%), hypertension (17.1% and 8.7%), hematopoietic thrombocytopenia (32.7% and 26.2%), and peripheral neuropathy (18.9% and 17.2%).
Fatal AEs were reported in 11.5% of patients in the KRd arm and 10.8% of those in the Rd arm.
Fatal AEs reported in at least 2 patients in the KRd arm included (in the KRd and Rd arms, respectively) cardiac disorders (2.6% and 2.3%), pneumonia (1.5% and 0.8%), sepsis (0.8% for both), myocardial infarction (0.8% and 0.5%), acute respiratory distress syndrome (0.8% and 0%), death (0.5% for both), and cardiac arrest (0.5% and 0.3%).
This trial was funded by Onyx Pharmaceuticals, Inc.
Adding carfilzomib (K) to treatment with lenalidomide and dexamethasone (Rd) can improve overall survival (OS) in patients with relapsed or refractory multiple myeloma (MM), according to research published in the Journal of Clinical Oncology.
Final results from the phase 3 ASPIRE trial showed that KRd reduced the risk of death by 21% and extended OS by 7.9 months, when compared to Rd.
In patients at first relapse, KRd was associated with an OS improvement of 11.4 months.
“Results from the final analysis of the phase 3 ASPIRE trial . . . are significant, as they further validate carfilzomib, lenalidomide, and dexamethasone as a standard-of-care regimen for patients with relapsed or refractory multiple myeloma,” said study author Keith Stewart, MBChB, of Mayo Clinic in Scottsdale, Arizona.
“Furthermore, these data showed that early use of carfilzomib, lenalidomide, and dexamethasone at first relapse provided nearly 1 additional year of survival for patients, regardless of prior treatment with bortezomib or transplant.”
ASPIRE enrolled 792 MM patients who had received a median of 2 prior therapies (range, 1-3). They were randomized to receive KRd (n=396) or Rd (n=396). Baseline characteristics were well balanced between the treatment arms.
Details on patients and treatment, as well as interim results from ASPIRE, were reported at the 2014 ASH Annual Meeting and published in NEJM in January 2015.
Treatment update
In the final analysis, there were 340 patients in the KRd arm and 358 in the Rd arm who stopped study treatment.
Reasons for discontinuation (in the KRd and Rd arms, respectively) were disease progression (n=188 and 224), adverse events (AEs, n=79 and 85), other reasons (n=61 and 35), withdrawn consent (n=10 and 12), and noncompliance (n=2 and 1).
A total of 182 patients in the KRd arm and 211 in the Rd arm received subsequent treatment for MM. These treatments were generally balanced between the KRd and Rd arms.
The median time to next treatment from the time of randomization was 39.0 months in the KRd arm and 24.4 months in the Rd arm (hazard ratio [HR]=0.65 P<0.001).
Survival
Interim ASPIRE data had shown a significant improvement in progression-free survival (PFS) and a trend toward improved OS in patients who received KRd. Now, researchers have observed a significant improvement in both endpoints with KRd.
The data cutoff for the final analysis was April 28, 2017. For PFS, the median follow-up was 48.8 months in the KRd arm and 48.0 months in the Rd arm.
The median PFS was 26.1 months in the KRd arm and 16.6 months in the Rd arm (9.5-month improvement, HR=0.66; P<0.001). The 3-year PFS rates were 38.2% and 28.4%, respectively. And the 5-year PFS rates were 25.6% and 17.3%, respectively.
The median follow-up for OS was 67.1 months. The median OS was 48.3 months in the KRd arm and 40.4 months in the Rd arm (7.9-month improvement, HR=0.79, P=0.0045).
The researchers also performed subgroup analyses according to prior lines of therapy, prior bortezomib exposure at first relapse, and prior transplant at first relapse.
In patients who had received 1 prior line of therapy, the median OS was 47.3 months in the KRd arm and 35.9 months in the Rd arm (11.4-month improvement, HR=0.81). For patients with 2 or more prior lines of therapy, the median OS was 48.8 months and 42.3 months, respectively (6.5-month improvement, HR=0.79).
Among patients with prior bortezomib exposure at first relapse, the median OS was 45.9 months in the KRd arm and 33.9 months in the Rd arm (12-month improvement, HR=0.82). Among patients without prior bortezomib exposure at first relapse, the median OS was 48.3 months and 40.4 months, respectively (7.9-month improvement, HR=0.80).
Among patients with prior transplant at first relapse, the median OS was 57.2 months in the KRd arm and 38.6 months in the Rd arm (18.6-month improvement, HR=0.71).
Safety
The incidence of treatment-emergent AEs was 98% in the KRd arm and 97.9% in the Rd arm. The incidence of grade 3 or higher AEs was 87% and 83.3%, respectively. The incidence of serious AEs was 65.3% and 56.8%, respectively.
Treatment discontinuation due to an AE occurred in 19.9% of patients in the KRd arm and 21.5% of patients in the Rd arm.
AEs of interest (in the KRd and Rd arms, respectively) included acute renal failure (9.2% and 7.7%), cardiac failure (7.1% and 4.1%), ischemic heart disease (6.9% and 4.6%), hypertension (17.1% and 8.7%), hematopoietic thrombocytopenia (32.7% and 26.2%), and peripheral neuropathy (18.9% and 17.2%).
Fatal AEs were reported in 11.5% of patients in the KRd arm and 10.8% of those in the Rd arm.
Fatal AEs reported in at least 2 patients in the KRd arm included (in the KRd and Rd arms, respectively) cardiac disorders (2.6% and 2.3%), pneumonia (1.5% and 0.8%), sepsis (0.8% for both), myocardial infarction (0.8% and 0.5%), acute respiratory distress syndrome (0.8% and 0%), death (0.5% for both), and cardiac arrest (0.5% and 0.3%).
This trial was funded by Onyx Pharmaceuticals, Inc.