MEETING NEWS MYELOMA
Final ASPIRE Results Confirm Survival Benefit With Carfilzomib Plus Lenalidomide and Dexamethasone in Relapsed / Refractory Myeloma
According to final results from the phase III ASPIRE study assessing patients with relapsed / refractory multiple myeloma ( MM ), adding the proteasome inhibitor carfilzomib to a lenalidomide and dexamethasone regimen improves response rates and overall survival ( OS ), without increasing the risk of adverse events ( AEs ).
“ The addition of carfilzomib resulted in a higher objective response rate , a tripling of the complete response rate , and significant and clinically relevant prolongation of both progression-free survival ( PFS ) and OS ,” reported lead author Keith Stewart , MBChB , MBA , of the Division of Hematology / Oncology at the Mayo Clinic in Scottsdale , Arizona , at the 2017 ASH Annual Meeting .
In earlier results , researchers found that the three-drug regimen significantly improved PFS , compared with lenalidomide and dexamethasone alone in patients with relapsed / refractory MM ; the latest results include a final OS analysis .
Adult patients with relapsed / refractory MM who had received one to three prior lines of therapy were included . Participants were randomized 1:1 to receive carfilzomib , lenalidomide , and dexamethasone ( n = 396 ) or the standard treatment of lenalidomide and dexamethasone ( n = 396 ) in 28-day cycles :
• lenalidomide 25 mg on days 1-21 of each cycle
Compared with patients treated with lenalidomidedexamethasone alone , those who also received carfilzomib had a longer median OS : 48.3 months ( range = 42.4-52.8 months ) versus 40.4 months ( range = 33.6-44.4 months ), for a 21 percent reduction in the risk of death ( hazard ratio [ HR ] = 0.79 ; 95 % CI 0.67-0.95 ; p = 0.004 ).
The authors also identified factors associated with longer OS among carfilzomib-treated patients , including a lower number of prior lines of therapy and disease stage ( per Revised International Staging System [ R-ISS ] score ).
For patients who received only one prior line of therapy , median OS was 11.4 months longer in the three- than two-drug group ( 47.3 vs . 35.9 months [ HR = 0.81 ; 95 % CI 0.62-1.06 ; p value not provided ]). For patients who received two or more prior lines of therapy , median OS was 6.5 months longer ( 48.8 vs . 42.3 months [ HR = 0.79 ; 95 % CI 0.62-0.99 ; p value not provided ]).
The survival benefit with carfilzomib also persisted regardless of prior exposure to bortezomib : Median OS was improved by 12 months in patients with prior bortezomib exposure ( 45.9 vs . 33.9 months [ HR = 0.82 ; 95 % CI 0.56-1.19 ]) and 7.9 months in those without ( 48.3 vs . 40.4 months [ HR = 0.80 ; 95 % CI 0.55-1.17 ]).
Median OS also was longer among patients who received carfilzomib despite R-ISS :
• dexamethasone 40 mg on days 1 , 8 , 15 , and 22 of each cycle
• carfilzomib administered as a 10-minute infusion at a starting dose of 20 mg / m 2 on days 1 and 2 of cycle 1 ; a target dose of 27 mg / m 2 on days 1 , 2 , 8 , 9 , 15 , and 16 during cycles 1-12 ; and 27 mg / m 2 on days 1 , 2 , 15 , and 16 during cycles 13-18
Patients were treated until withdrawal of consent , disease progression , or unacceptable toxicity . After 18 treatment cycles , patients in the carfilzomib arm received treatment with lenalidomide and dexamethasone alone .
As of April 28 , 2017 ( data cutoff ), patients had been followed for a median of 67 months in each arm ( ranges not provided ).
• R-ISS stage I : not reached for carfilzomib-treated patients vs . 58.0 months for lenalidomide and dexamethasone ( HR = 0.49 ; 95 % CI 0.26-0.92 ; p value not provided )
• R-ISS stage II : 45.4 months vs . 41.2 months ( HR = 0.86 ; 95 % CI 0.68-1.10 ; p value not provided )
• R-ISS stage III : 23.3 months vs . 18.8 months ( HR = 1.05 ; 95 % CI 0.66-1.68 ; p value not provided )
As seen in TABLE 3 , safety profiles were similar between both treatment arms . Fatal AEs were reported in 11.5 percent of carfilzomibtreated patients and 10.5 percent of those who received lenalidomide
TABLE 3 . Safety Profile
Carfilzomib , lenalidomide , dexamethasone ( n = 396 )
Lenalidomide , dexamethasone ( n = 396 )
Treatment discontinuation due to an AE 19.9 % 21.5 % Any-grade AEs 98.0 % 97.9 % Grade ≥3 AEs 87.0 % 83.0 % Grade 5 AEs 11.5 % 10.5 % AE = adverse event
26 Focus on Lymphoma & Myeloma