Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone.
OBJECTIVE
High-dose melphalan and autologous stem cell transplantation is currently the treatment of choice for selected patients with AL amyloidosis; however, new treatments are needed for patients who are ineligible for or relapse after this procedure. Bortezomib is a proteasome inhibitor with proven activity in multiple myeloma, and the addition of dexamethasone results in superior outcome. We evaluated the activity and feasibility of the combination of bortezomib and dexamethasone (BD) in patients with AL amyloidosis.


METHODS
Consecutive patients with histologically proven, symptomatic AL amyloidosis were treated with BD.


RESULTS
Eighteen patients, including seven who had relapsed or progressed after previous therapies were treated with BD. Eleven (61%) patients had two or more organs involved; kidneys and heart were affected in 14 and 15 patients, respectively. The majority of patients had impaired performance status and high brain natriuretic peptide values; serum creatinine was elevated in six patients. Among evaluable patients, 94% had a hematologic response and 44% a hematologic complete response, including all five patients who had not responded to prior high dose dexamethasone-based treatment and one patient under dialysis. Five patients (28%) had a response in at least one affected organ. Hematologic responses were rapid (median 0.9 months) and median time to organ response was 4 months. Neurotoxicity, fatigue, peripheral edema, constipation and exacerbation of postural hypotension were manageable although necessitated dose adjustment or treatment discontinuation in 11 patients.


CONCLUSIONS
The combination of BD is feasible in patients with AL amyloidosis. Patients achieve a rapid hematologic response and toxicity can be managed with close follow-up and appropriate dose adjustment. This treatment may be a valid option for patients with severe heart or kidney impairment.
Kastritis
Efstathios
E
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, School of Medicine, Athens, Greece.
Anagnostopoulos
Athanasios
A
Roussou
Maria
M
Toumanidis
Savvas
S
Pamboukas
Constantinos
C
Migkou
Magdalini
M
Tassidou
Anna
A
Xilouri
Irini
I
Delibasi
Sossana
S
Psimenou
Erasmia
E
Mellou
Sofia
S
Terpos
Evangelos
E
Nanas
John
J
Dimopoulos
Meletios A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone