Contributions
Abstract: PB2183
Type: Publication Only
Background
The proteasome inhibitor carfilzomib was recently approved for treatment of RRMM. In the period before approval, drugs can be provided to critically ill patients with few treatment options, through expanded access programs.
Aims
This retrospective study of patients who received carfilzomib before marketing, was designed to describe the patients’ characteristics and their corresponding treatment responses. An additional intention was to use the real-life experience to highlight a possible benefit of making new drugs available before marketing approval.
Methods
33 Norwegian patients received carfilzomib through an NPP in the period from March 2015 to January 2016, for RRMM within 10 different Norwegian hospitals. The patient journals were printed and sent from the respective hospitals to Oslo Myeloma Center. Baseline values and treatment responses was assessed and entered into our myeloma database. Statistical analysis was done to determine response rates and time to event outcomes.
Results
The participants had received a median of 6 (1-11) previous lines of therapy, frequently including bortezomib (100%) and thalidomide and/or lenalidomide (97%), which was refractory in respectively 63,5% and 65,6% of the exposed. The most frequently used regimen was carfilzomib and dexamethasone (Kd). Response rates showed a median overall response rate (ORR) of 25% and a clinical benefit rate (CBR) of 44,4%. The median progression free survival (PFS) was 3.0 months, with a median overall survival (OS) of 7.0 months. Patients who achieved at least partial response (PR) showed a significantly longer progression free survival with a median PFS of 8,5 months, and patients who received lenalidomide in addition to carfilzomib (KRd) showed a significantly better response with an ORR of 55,6%. Among the patients refractory to bortezomib, ORR was 10,7% and CBR 28,6%; among the patients refractory to thalidomide/lenalidomide ORR was 14,8% and CBR 29%. The patients refractory to both bortezomib and thalidomide/lenalidomide demonstrated ORR of 10,5% and CBR of 31,6%. Adverse events occurred in 90,6% of the patients, with 59,4% experiencing one or more cytopenias, 25% fatigue, 21,9% dyspnea, 18,8% cardiovascular complication and 18,8% kidney failure. 3/32 (9,4%) of patients discontinued treatment owing to adverse events. 2/33 died before ending carfilzomib, and 25/33 (75%) was dead by the time of the end of study. Carfilzomib was not considered as a direct cause of death in any patient.
Conclusion
MM is incurable in most cases, and the response is inversely correlated with the number of treatment lines. The majority of our real-life patients had advanced MM and where heavily treated prior to carfilzomib. Still a significant part of the patients benefited from the treatment in terms of prolonged PFS (3 months) and OS (7 months), with significantly increased PFS of 8,5 months, among those who experienced PR or better. A superior response was shown by those treated with lenalidomid in addition to carfilzomib (KRd). The results confirms the advantage of access to medicines prior to marketing authorization.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma, Therapy
Abstract: PB2183
Type: Publication Only
Background
The proteasome inhibitor carfilzomib was recently approved for treatment of RRMM. In the period before approval, drugs can be provided to critically ill patients with few treatment options, through expanded access programs.
Aims
This retrospective study of patients who received carfilzomib before marketing, was designed to describe the patients’ characteristics and their corresponding treatment responses. An additional intention was to use the real-life experience to highlight a possible benefit of making new drugs available before marketing approval.
Methods
33 Norwegian patients received carfilzomib through an NPP in the period from March 2015 to January 2016, for RRMM within 10 different Norwegian hospitals. The patient journals were printed and sent from the respective hospitals to Oslo Myeloma Center. Baseline values and treatment responses was assessed and entered into our myeloma database. Statistical analysis was done to determine response rates and time to event outcomes.
Results
The participants had received a median of 6 (1-11) previous lines of therapy, frequently including bortezomib (100%) and thalidomide and/or lenalidomide (97%), which was refractory in respectively 63,5% and 65,6% of the exposed. The most frequently used regimen was carfilzomib and dexamethasone (Kd). Response rates showed a median overall response rate (ORR) of 25% and a clinical benefit rate (CBR) of 44,4%. The median progression free survival (PFS) was 3.0 months, with a median overall survival (OS) of 7.0 months. Patients who achieved at least partial response (PR) showed a significantly longer progression free survival with a median PFS of 8,5 months, and patients who received lenalidomide in addition to carfilzomib (KRd) showed a significantly better response with an ORR of 55,6%. Among the patients refractory to bortezomib, ORR was 10,7% and CBR 28,6%; among the patients refractory to thalidomide/lenalidomide ORR was 14,8% and CBR 29%. The patients refractory to both bortezomib and thalidomide/lenalidomide demonstrated ORR of 10,5% and CBR of 31,6%. Adverse events occurred in 90,6% of the patients, with 59,4% experiencing one or more cytopenias, 25% fatigue, 21,9% dyspnea, 18,8% cardiovascular complication and 18,8% kidney failure. 3/32 (9,4%) of patients discontinued treatment owing to adverse events. 2/33 died before ending carfilzomib, and 25/33 (75%) was dead by the time of the end of study. Carfilzomib was not considered as a direct cause of death in any patient.
Conclusion
MM is incurable in most cases, and the response is inversely correlated with the number of treatment lines. The majority of our real-life patients had advanced MM and where heavily treated prior to carfilzomib. Still a significant part of the patients benefited from the treatment in terms of prolonged PFS (3 months) and OS (7 months), with significantly increased PFS of 8,5 months, among those who experienced PR or better. A superior response was shown by those treated with lenalidomid in addition to carfilzomib (KRd). The results confirms the advantage of access to medicines prior to marketing authorization.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma, Therapy