Efficacy of the Combination of Bortezomib and Dexamethasone in Systemic AL Amyloidosis.

AL amyloidosis is characterized by misfolding of structurally unstable light chains that form deposits in various organs thereby causing impaired organ function. Treatment of AL amyloidosis remains challenging and is primarily directed towards the underlying abnormal plasma cell clone. Novel agents with proven efficacy in multiple myeloma like the proteasome inhibitor bortezomib have also shown initial promising results in patients with AL amyloidosis, but its value needs to be further established. In this retrospective analysis, we have collected data regarding efficacy and tolerability of treatment with bortezomib plus dexamethasone in patients with AL amyloidosis.

25 patients with histologically proven systemic AL amyloidosis were included in this analysis. All patients received bortezomib at a standard dose of 1.3mg/m² (days 1, 4, 8, 11 of a 3-week cycle) in combination with dexamethasone (8mg to 20mg administered on the day of bortezomib and the day after). Routine clinical and laboratory parameters including evaluation were obtained on a monthly basis.

Patients (male n=13, female n=12) were at a median age of 57 years (range 42-83), and 17 patients (68%) received bortezomib/dexamethasone as their first line treatment. The majority of patients had an ECOG performance status of < 2. Twelve patients (48%) had only one organ involved, whereas > 2 organs were involved in 6 patients (24%). Organs most frequently involved were kidneys (100%), heart (28%), liver (12%) and the gastrointestinal tract (12%). At the time of analysis, a median of 3 cycles of bortezomib/dexamethasone (range, 1 to 8) have been administered. A hematologic response was observed in 14 patients (56%) including 5 patients (20%) qualifying for a complete response (CR). All CR patients received bortezomib/dexamethasone as their first line treatment, and parameters of organ function also improved in these patients. Median overall survival has not yet been reached after a median follow-up of 12 months. Grade 3 and 4 toxicities were rare and consisted predominantly of transient thrombocytopenia. Grade 2 neurotoxicity was observed in 24% of patients. Other grade 1/2 toxicities observed at higher frequencies included hypotension (16%), edema (16%), and fatigue (12%).

Our results confirm the activity of bortezomib/dexamethasone in patients with AL amyloidosis (hematologic response rate 56% including a 20% CR rate).

Ludwig:Celgene: Honoraria; Mundipharma: Honoraria; AMGEN: Honoraria; Ortho-Biotech : Honoraria; Janssen-Cilag: Research Funding; Roche: Honoraria.