Data from a secondary analysis of the pivotal phase 3 ASPIRE trial that showed Carfilzomib ( Kyprolis ) for injection in combination with Lenalidomide ( Revlimid ) and Dexamethasone ( KRd) improved progression-free survival ( PFS ) and overall response rate ( ORR ) compared to Lenalidomide and Dexamethasone ( Rd ) alone in patients with relapsed multiple myeloma with early disease progression after initial therapy or transplant, were presented at the 52nd Annual Meeting of the American Society of Clinical Oncology ( ASCO ).
The analysis showed that patients relapsing within one year of initial therapy treated with KRd ( n=87 ) experienced a median progression-free survival of 24.1 months versus 12.5 months in those treated with Rd ( n=72 ) ( hazard ratio, HR=0.75; 95% CI: 0.50-1.13 ).
In addition, ORR in the KRd arm was 79.3% versus 61.1% in the Rd arm.
Patients relapsing early after first prior transplant treated with KRd ( n=48 ) experienced a median progression-free survival of 17.3 months versus 11.1 months in those treated with Rd ( n=49 ) ( HR=0.87; 95% CI: 0.54-1.41 ).
In addition, the ORR in the KRd arm was 83.3% versus 61.2% in the Rd arm.
Grade 3 adverse events that occurred at least 5% more frequently in the KRd arm compared to the Rd arm in either subgroup were hypokalemia, neutropenia, febrile neutropenia, hypophosphatemia and respiratory tract infection.
An exploratory sub-group analysis assessed the efficacy and safety of KRd compared with Rd alone in 159 patients with multiple myeloma who had relapsed less than or equal to one year from their first treatment.
A second sub-group analysis examined 97 patients with multiple myeloma who had relapsed less than or equal to one year from prior transplant.
In patients who had relapsed less than or equal to one year from their first treatment, median progression-free survival in the KRd arm was 24.1 months versus 12.5 months for Rd ( HR=0.75; 95% CI: 0.50-1.13 ), and ORR was 79.3% for KRd versus 61.1% for Rd.
In addition, 21.8% of patients in the KRd arm experienced a complete response versus 4.2% treated with Rd.
In patients who had relapsed less than or equal to one year after transplant, median progression-free survival in the KRd arm was 17.3 months versus 11.1 months for Rd ( HR=0.87; 95% CI: 0.54-1.41 ), and ORR was 83.3% for KRd versus 61.2% for Rd. Complete responses in the KRd and Rd arms were 12.5% and 4.1%, respectively.
Grade 3 or higher adverse events that occurred in greater than or equal to 5% more frequently in KRd than Rd in both groups were hypokalemia, neutropenia, febrile neutropenia, hypophosphatemia and respiratory tract infection.
In the international, randomized Phase 3 ASPIRE ( CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma ) trial patients were randomized to receive Carfilzomib ( 20 mg/m2 on days 1 and 2 of cycle one only, escalating to 27 mg/m2 on days 8, 9, 15 and 16 of cycle one and continuing on days 1, 2, 8, 9, 15 and 16 of subsequent cycles ), in addition to a standard dosing schedule of Lenalidomide ( 25 mg per day for 21 days on, 7 days off ) and low-dose Dexamethasone ( 40 mg per week in four-week cycles ), versus Lenalidomide and low-dose Dexamethasone alone.
The study randomized 792 patients at sites in North America, Europe and Israel.
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. Carfilzomib has been shown to block proteasomes, leading to an excessive build-up of proteins within cells. In some cells, Carfilzomib can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins. ( Xagena )
Source: Amgen, 2016