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Can Pomalidomide Plus Dexamethasone “ Rescue ” Patients With Relapsed / Refractory Amyloid Light-Chain Amyloidosis ?
Patients with amyloid light-chain ( AL ) amyloidosis are often treated upfront with combinations of alkylating agents and bortezomib ; when they don ’ t respond to this regimen or relapse , available active salvage options are limited .
In a phase II study published in Blood , treatment with the immunomodulatory agent pomalidomide plus dexamethasone resulted in a 68 percent response rate and a median overall survival ( OS ) and progression-free survival ( PFS ) of 26 months and 16 months , respectively .
“ Our study showed that pomalidomide is effective in patients with AL amyloidosis who were previously exposed to alkylators , proteasome inhibitors , and lenalidomide . Even at an advanced stage in the course of the disease , response to rescue therapy improved survival ,” lead author Giovanni Palladini , MD , PhD , from the Amyloidosis Research and Treatment Center at the University of Pavia in Italy , told ASH Clinical News . “ Importantly , responses were rapid and achieved after one cycle in 53 percent of responders .”
The study included 28 patients ( median age = 64 years ; range = 41-80 years ) who were previously treated with :
• bortezomib ( 96 %, n = 27 )
• melphalan ( 75 %, n = 21 ) tolerated dose was 4 mg , so the remaining 22 patients received pomalidomide 4 mg plus dexamethasone 20 mg ( in the case of severe fluid retention and / or repetitive ventricular arrhythmia ; n = 12 , 43 %) or 40 mg weekly . A total of 227 cycles were delivered during the study period , with a median of six cycles per patient ( range = 1-30 cycles ).
After three treatment cycles , 61 percent of patients ( n = 17 ) achieved a hematologic response ( primary endpoint ), including partial response ( PR ; n = 10 , 36 %) and very good PR ( VGPR ; n = 7 ,
25 %). Nineteen patients achieved a best response by cycle seven ( 68 %; 95 % CI 49-83 ), which included complete response ( n = 1 , 4 %), VGPR ( n = 7 , 25 %), and PR ( n = 11 , 39 %), suggesting that responses were achieved rapidly .
Hematologic response was associated
• cyclophosphamide ( 68 %, n = 19 )
• lenalidomide ( 25 %, n = 7 )
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• thalidomide ( 14 %, n = 4 )
• ixazomib ( 14 %, n = 4 )
• bendamustine ( 11 %, n = 3 )
All patients had a difference between amyloidogenic ( involved ) and uninvolved free light chain of > 50 mg / L and adequate renal function ( defined as an estimated glomerular filtration rate of ≥30 mL / min ) and cardiac function ( defined as a New York Heart Association class of < 4 ).
Most patients were male ( 57 %, n = 16 ), and half had an Eastern Cooperative Oncology Group performance status of 2 ( n = 14 ), and had cardiac stage 2 function ( n = 14 ). Patients were enrolled between June 2012 and November 2013 , a median of 16 months after diagnosis .
In a 3 + 3 dose-escalation design , three patients received pomalidomide 2 mg / day and three patients received 4 mg / day . The maximum
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