CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (KCYD) IN ELDERLY NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM) PATIENTS: INITIAL RESULTS OF A PHASE 1 STUDY
(Abstract release date: 05/19/16)
EHA Library. Bringhen S. 06/09/16; 132809; E1260
Disclosure(s): Honoraria from Celgene, Janssen-Cilag; Advisory board for Mundipharma.
Dr. Sara Bringhen
Contributions
Contributions
Abstract
Abstract: E1260
Type: Eposter Presentation
Background
The combination of carfilzomib at the dose 20/36 mg/m2, cyclophosphamide and dexamethasone has been demonstrated to be well tolerated and highly effective (Bringhen S. et al, Blood 2014; 124:63-9). A further dose escalation could improve clinical efficacy. Herein we present initial results of the dose-escalation phase 1 portion of a multicenter, phase 1/2 study evaluating the safety and the efficacy of the combination KCyd in elderly NDMM patients (pts).
Aims
The primary objective was to determine the maximum tolerated dose. The secondary objectives were to determine the safety and the efficacy of KCyd, including response rate, time to progression, progression free survival, time to next therapy and overall survival. ated results will be presented.
Methods
Newly diagnosed pts not eligible for autologous stem cell transplantation due to age or co-morbidities were eligible. Carfilzomib was administered intravenously on days 1,2,8,9,15,16, cyclophosphamide was administered orally on days 1,8,15 and dexamethasone was administered orally once weekly. Dose-escalation used a standard 3+3 schema with dose-limiting toxicities (DLTs) assessed during cycle 1. All pts received carfilzomib at 20 mg/m2 on days 1 and 2 of cycle 1. Beginning on day 8 of cycle 1, carfilzomib was escalated in 3 successive dose levels from 45 to 70 mg/m2 in combination with the standard doses of cyclophosphamide 300 mg/m2 and dexamethasone 40 mg. KCyd induction was administered for 9 28-day cycles. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed according to the modified International Uniform Response Criteria.
Results
Between June 2014 and March 2015, 9 pts were enrolled in the completed phase 1 dose-escalation portion of the study. Median age was 74 years (range 67-82), 44% had ISS stage III, 67% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p or amp1]. No DLTs were observed in the 3 pts of cohort 1, with carfilzomib at 45 mg/m2. In cohort 2 carfilzomib was escalated to 56 mg/m2 and 1/6 pt had a DLT with acute kidney injury. Therefore, the MTD of carfilzomib was established at 56 mg/m2. Drug-related AEs occurring in >20% of pts included anaemia (56%), fever (44%), thrombocytopenia (33%), diarrhoea (33%), vomiting (33%), infections (33%), hypertension (33%), heart failure (22%), acute kidney injury (22%). Grade 3 AEs occurring in >10% of pts included anaemia (22%), infections (22%), acute kidney injury (22%) and heart failure (11%). Only 1 grade 4 AE was reported (thrombocytopenia). Six pts completed induction treatment, 2 pts discontinued treatment due to AEs and 1 pt due to pt decision.After a median follow-up of 14.2 months, 2 pts achieved a complete response (CR), 4 pts a very good partial response (VGPR) and 3 pts a partial response (PR), for an overall response rate of 100%, at least VGPR of 66% and at least CR of 22%. No progressive disease or death occurred during induction.
Conclusion
The MTD of carfilzomib was established at 56 mg/m2. KCyd combination given to untreated, symptomatic, elderly pts with myeloma is well tolerated and highly effective with an overall response rate of 100%, including a CR rate of 22%. Enrollment in the phase 2 portion of the study is ongoing and updated results will be presented.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Proteasome inhibitor
Type: Eposter Presentation
Background
The combination of carfilzomib at the dose 20/36 mg/m2, cyclophosphamide and dexamethasone has been demonstrated to be well tolerated and highly effective (Bringhen S. et al, Blood 2014; 124:63-9). A further dose escalation could improve clinical efficacy. Herein we present initial results of the dose-escalation phase 1 portion of a multicenter, phase 1/2 study evaluating the safety and the efficacy of the combination KCyd in elderly NDMM patients (pts).
Aims
The primary objective was to determine the maximum tolerated dose. The secondary objectives were to determine the safety and the efficacy of KCyd, including response rate, time to progression, progression free survival, time to next therapy and overall survival. ated results will be presented.
Methods
Newly diagnosed pts not eligible for autologous stem cell transplantation due to age or co-morbidities were eligible. Carfilzomib was administered intravenously on days 1,2,8,9,15,16, cyclophosphamide was administered orally on days 1,8,15 and dexamethasone was administered orally once weekly. Dose-escalation used a standard 3+3 schema with dose-limiting toxicities (DLTs) assessed during cycle 1. All pts received carfilzomib at 20 mg/m2 on days 1 and 2 of cycle 1. Beginning on day 8 of cycle 1, carfilzomib was escalated in 3 successive dose levels from 45 to 70 mg/m2 in combination with the standard doses of cyclophosphamide 300 mg/m2 and dexamethasone 40 mg. KCyd induction was administered for 9 28-day cycles. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed according to the modified International Uniform Response Criteria.
Results
Between June 2014 and March 2015, 9 pts were enrolled in the completed phase 1 dose-escalation portion of the study. Median age was 74 years (range 67-82), 44% had ISS stage III, 67% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p or amp1]. No DLTs were observed in the 3 pts of cohort 1, with carfilzomib at 45 mg/m2. In cohort 2 carfilzomib was escalated to 56 mg/m2 and 1/6 pt had a DLT with acute kidney injury. Therefore, the MTD of carfilzomib was established at 56 mg/m2. Drug-related AEs occurring in >20% of pts included anaemia (56%), fever (44%), thrombocytopenia (33%), diarrhoea (33%), vomiting (33%), infections (33%), hypertension (33%), heart failure (22%), acute kidney injury (22%). Grade 3 AEs occurring in >10% of pts included anaemia (22%), infections (22%), acute kidney injury (22%) and heart failure (11%). Only 1 grade 4 AE was reported (thrombocytopenia). Six pts completed induction treatment, 2 pts discontinued treatment due to AEs and 1 pt due to pt decision.After a median follow-up of 14.2 months, 2 pts achieved a complete response (CR), 4 pts a very good partial response (VGPR) and 3 pts a partial response (PR), for an overall response rate of 100%, at least VGPR of 66% and at least CR of 22%. No progressive disease or death occurred during induction.
Conclusion
The MTD of carfilzomib was established at 56 mg/m2. KCyd combination given to untreated, symptomatic, elderly pts with myeloma is well tolerated and highly effective with an overall response rate of 100%, including a CR rate of 22%. Enrollment in the phase 2 portion of the study is ongoing and updated results will be presented.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Proteasome inhibitor
Abstract: E1260
Type: Eposter Presentation
Background
The combination of carfilzomib at the dose 20/36 mg/m2, cyclophosphamide and dexamethasone has been demonstrated to be well tolerated and highly effective (Bringhen S. et al, Blood 2014; 124:63-9). A further dose escalation could improve clinical efficacy. Herein we present initial results of the dose-escalation phase 1 portion of a multicenter, phase 1/2 study evaluating the safety and the efficacy of the combination KCyd in elderly NDMM patients (pts).
Aims
The primary objective was to determine the maximum tolerated dose. The secondary objectives were to determine the safety and the efficacy of KCyd, including response rate, time to progression, progression free survival, time to next therapy and overall survival. ated results will be presented.
Methods
Newly diagnosed pts not eligible for autologous stem cell transplantation due to age or co-morbidities were eligible. Carfilzomib was administered intravenously on days 1,2,8,9,15,16, cyclophosphamide was administered orally on days 1,8,15 and dexamethasone was administered orally once weekly. Dose-escalation used a standard 3+3 schema with dose-limiting toxicities (DLTs) assessed during cycle 1. All pts received carfilzomib at 20 mg/m2 on days 1 and 2 of cycle 1. Beginning on day 8 of cycle 1, carfilzomib was escalated in 3 successive dose levels from 45 to 70 mg/m2 in combination with the standard doses of cyclophosphamide 300 mg/m2 and dexamethasone 40 mg. KCyd induction was administered for 9 28-day cycles. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed according to the modified International Uniform Response Criteria.
Results
Between June 2014 and March 2015, 9 pts were enrolled in the completed phase 1 dose-escalation portion of the study. Median age was 74 years (range 67-82), 44% had ISS stage III, 67% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p or amp1]. No DLTs were observed in the 3 pts of cohort 1, with carfilzomib at 45 mg/m2. In cohort 2 carfilzomib was escalated to 56 mg/m2 and 1/6 pt had a DLT with acute kidney injury. Therefore, the MTD of carfilzomib was established at 56 mg/m2. Drug-related AEs occurring in >20% of pts included anaemia (56%), fever (44%), thrombocytopenia (33%), diarrhoea (33%), vomiting (33%), infections (33%), hypertension (33%), heart failure (22%), acute kidney injury (22%). Grade 3 AEs occurring in >10% of pts included anaemia (22%), infections (22%), acute kidney injury (22%) and heart failure (11%). Only 1 grade 4 AE was reported (thrombocytopenia). Six pts completed induction treatment, 2 pts discontinued treatment due to AEs and 1 pt due to pt decision.After a median follow-up of 14.2 months, 2 pts achieved a complete response (CR), 4 pts a very good partial response (VGPR) and 3 pts a partial response (PR), for an overall response rate of 100%, at least VGPR of 66% and at least CR of 22%. No progressive disease or death occurred during induction.
Conclusion
The MTD of carfilzomib was established at 56 mg/m2. KCyd combination given to untreated, symptomatic, elderly pts with myeloma is well tolerated and highly effective with an overall response rate of 100%, including a CR rate of 22%. Enrollment in the phase 2 portion of the study is ongoing and updated results will be presented.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Proteasome inhibitor
Type: Eposter Presentation
Background
The combination of carfilzomib at the dose 20/36 mg/m2, cyclophosphamide and dexamethasone has been demonstrated to be well tolerated and highly effective (Bringhen S. et al, Blood 2014; 124:63-9). A further dose escalation could improve clinical efficacy. Herein we present initial results of the dose-escalation phase 1 portion of a multicenter, phase 1/2 study evaluating the safety and the efficacy of the combination KCyd in elderly NDMM patients (pts).
Aims
The primary objective was to determine the maximum tolerated dose. The secondary objectives were to determine the safety and the efficacy of KCyd, including response rate, time to progression, progression free survival, time to next therapy and overall survival. ated results will be presented.
Methods
Newly diagnosed pts not eligible for autologous stem cell transplantation due to age or co-morbidities were eligible. Carfilzomib was administered intravenously on days 1,2,8,9,15,16, cyclophosphamide was administered orally on days 1,8,15 and dexamethasone was administered orally once weekly. Dose-escalation used a standard 3+3 schema with dose-limiting toxicities (DLTs) assessed during cycle 1. All pts received carfilzomib at 20 mg/m2 on days 1 and 2 of cycle 1. Beginning on day 8 of cycle 1, carfilzomib was escalated in 3 successive dose levels from 45 to 70 mg/m2 in combination with the standard doses of cyclophosphamide 300 mg/m2 and dexamethasone 40 mg. KCyd induction was administered for 9 28-day cycles. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed according to the modified International Uniform Response Criteria.
Results
Between June 2014 and March 2015, 9 pts were enrolled in the completed phase 1 dose-escalation portion of the study. Median age was 74 years (range 67-82), 44% had ISS stage III, 67% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p or amp1]. No DLTs were observed in the 3 pts of cohort 1, with carfilzomib at 45 mg/m2. In cohort 2 carfilzomib was escalated to 56 mg/m2 and 1/6 pt had a DLT with acute kidney injury. Therefore, the MTD of carfilzomib was established at 56 mg/m2. Drug-related AEs occurring in >20% of pts included anaemia (56%), fever (44%), thrombocytopenia (33%), diarrhoea (33%), vomiting (33%), infections (33%), hypertension (33%), heart failure (22%), acute kidney injury (22%). Grade 3 AEs occurring in >10% of pts included anaemia (22%), infections (22%), acute kidney injury (22%) and heart failure (11%). Only 1 grade 4 AE was reported (thrombocytopenia). Six pts completed induction treatment, 2 pts discontinued treatment due to AEs and 1 pt due to pt decision.After a median follow-up of 14.2 months, 2 pts achieved a complete response (CR), 4 pts a very good partial response (VGPR) and 3 pts a partial response (PR), for an overall response rate of 100%, at least VGPR of 66% and at least CR of 22%. No progressive disease or death occurred during induction.
Conclusion
The MTD of carfilzomib was established at 56 mg/m2. KCyd combination given to untreated, symptomatic, elderly pts with myeloma is well tolerated and highly effective with an overall response rate of 100%, including a CR rate of 22%. Enrollment in the phase 2 portion of the study is ongoing and updated results will be presented.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Proteasome inhibitor
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