CLINICAL NEWS
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
ASHClinicalNews . org
CLINICAL NEWS
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 immunomodula-
tory agent pomalidomide plus dexa-
methasone 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 pomalid-
omide 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 au-
thor Giovanni Palladini, MD, PhD,
from the Amyloidosis Research and
Treatment Center at the University of
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