Contributions
Abstract: PB2223
Type: Publication Only
Background
Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone.
Aims
In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, whose prognosis is particularly severe.
Methods
27 patients (16 M/11 F), with rrMM, median age at diagnosis 63 years (r. 47-79), median age at start of treatment 66 years (r. 53-83) treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 4 (r 1-12).
ISS was equally distributed, and cytogenetic was evaluable in 8 patients, and in particular one del13q14 1q gain, one del13q14 and one t(11;14). All patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 59% (16/27) of them had undergone at least to a single autologous SCT.
Results
According to IMWG criteria, after a median follow-up of 3 months (r.1-13), ORR was 66,7% (14/21: 8 VGPR, 6 PR) with 3 progressive diseases (PD) and 2 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 1 patient, KRD was, after having achieved at least a PR, a bridge to second autologous SCT.
Median time to response was 2 months (r.1-4), median OS from diagnosis was 51 months (r. 9-170), median OS from start of Carfilzomib was 3 months (r. 1-13).
Carfilzomib was well tolerated, with grade 2 anemia in 33% (9/27) of patients, successfully managed by ESAs, without necessity of blood transfusions; 18% (5/27) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 29% (8/27) grade 2, 18% (5/27) grade 3 and 7% (2/27) grade 4 thrombocytopenia, without hemorrhagic events and necessity of transfusions. Concerning severe extra-hematologic toxicity, it was observed pneumonia in 44% (12/27) of patients, treated by common antibiotic drugs; hypertension (grade 2-3) in 33% (9/27) of patients; arrhythmias in 7% (2/27) of patients; dyspnea in 11% (3/27) of patients; fatigue in 29% (8/27) of patients. All patients were carefully monitored by expert cardiologists of our deparment.
Conclusion
KRD has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Autologous bone marrow transplant, Multiple Myeloma, Proteasome inhibitor, Supportive care
Abstract: PB2223
Type: Publication Only
Background
Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone.
Aims
In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, whose prognosis is particularly severe.
Methods
27 patients (16 M/11 F), with rrMM, median age at diagnosis 63 years (r. 47-79), median age at start of treatment 66 years (r. 53-83) treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 4 (r 1-12).
ISS was equally distributed, and cytogenetic was evaluable in 8 patients, and in particular one del13q14 1q gain, one del13q14 and one t(11;14). All patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 59% (16/27) of them had undergone at least to a single autologous SCT.
Results
According to IMWG criteria, after a median follow-up of 3 months (r.1-13), ORR was 66,7% (14/21: 8 VGPR, 6 PR) with 3 progressive diseases (PD) and 2 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 1 patient, KRD was, after having achieved at least a PR, a bridge to second autologous SCT.
Median time to response was 2 months (r.1-4), median OS from diagnosis was 51 months (r. 9-170), median OS from start of Carfilzomib was 3 months (r. 1-13).
Carfilzomib was well tolerated, with grade 2 anemia in 33% (9/27) of patients, successfully managed by ESAs, without necessity of blood transfusions; 18% (5/27) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 29% (8/27) grade 2, 18% (5/27) grade 3 and 7% (2/27) grade 4 thrombocytopenia, without hemorrhagic events and necessity of transfusions. Concerning severe extra-hematologic toxicity, it was observed pneumonia in 44% (12/27) of patients, treated by common antibiotic drugs; hypertension (grade 2-3) in 33% (9/27) of patients; arrhythmias in 7% (2/27) of patients; dyspnea in 11% (3/27) of patients; fatigue in 29% (8/27) of patients. All patients were carefully monitored by expert cardiologists of our deparment.
Conclusion
KRD has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Autologous bone marrow transplant, Multiple Myeloma, Proteasome inhibitor, Supportive care