Abstract 4614

Treatment of patients (pts) with systemic AL Amyloidosis remains challenging and organ dysfunctions improve in not more than 1/3 of cases with standard treatment. Bortezomib has been reported to have activity in this disease, where the misfolded protein may render the amyloidogenic plasma cells particularly vulnerable to proteasome inhibition.

To evaluate the feasibility and efficacy of Bortezomib, we report our single center experience with Bortezomib-containing regimens in pts with AL Amyloidosis. Hematologic responses and functional organ responses were evaluated according to the 2005 International Society of Amyloidosis criteria (Gertz et al, Am J Hematol 2005). Complete hematologic response (CR) was defined as normalization of the free light chain ratio with no evidence of a monoclonal protein by immunofixation and partial response (PR) as a 50% reduction in M-spike or absolute light chain level; moreover, dFLC (difference between involved and uninvolved free light chain) < 40 mg/L defined a very good PR (VGPR). A cardiac response was also defined by NT-proBNP criteria (>30% and >300 mg/L decrease in pts with baseline NT-proBNP > 650 mg/L).

Since May 2010, 21 consecutive pts with AL Amyloidosis were treated with Bortezomib-containing regimens at our center: Bortezomib-Dexamethasone (Vel-D), 5 pts; Cyclophosphamide-Bortezomib-Dexamethasone (CyBOR-D), 14 pts; Bortezomib-Melphalan-Prednisone (VMP),2 pts. Median age was 62 years (43-74). Fifteen pts were treated upfront, while 7 had refractory or relapsed disease after several lines of therapy. According to the cardiac staging system based on NT-proBNP and troponin I, 6 (29%) pts were stage 1, 9 (42%) stage 2 and 6 (29%) stage 3. At the time of this report 9 pts, still on treatment, have received less than 4 cycles and are not yet evaluable for response. Twelve pts received a median of 5,5 cycles (range, 4–8) and were analysed for outcome. Five received Vel-D, 5 CyBOR-D and 2 VMP. Eight were treated upfront and 4 after previous treatment (including ASCT in 3). Ten (83%) had renal, 6 (50%) cardiac, 2 (17%) soft tissue, 3 (25%) nerve, 2 (17%) gastrointestinal tract and 1 (8%) liver involvement. Four pts (33%) achieved hematologic CR, 3 (25%) VGPR and 3 (25%) PR (overall hematologic response rate (ORR) 83%), with no difference in ORR between Vel-D and CyBOR-D. One pt had a stable disease and 1, treated for second relapse, had progressive disease and died. Median time to response was 2 months (2-4). One pt underwent HD-MEL after PR with Vel-D and 3 pts had peripheral blood stem cells collected (soon after diagnosis (2) and after initial response (1)) and cryopreserved (to perform ASCT if unsatisfactory response or relapse). Four of eight evaluable pts (50%) had a renal response and 4/6 (66%) had a cardiac response. Hematologic toxicity was negligible; 6 pts had significant extra-hematologic complications, including 3 heart failure, 2 interstitial and 1 bacterial pneumonia, 1 Staph. sepsis, 1 H1N1 virus infection, 1 CMV reactivation, 1 grade 3 neuropathy and 1 grade 3 diarrhoea. No pts died because of toxicity. CyBor-D was apparently better tolerated.

In this unselected series of systemic AL Amyloidosis, Bortezomib-containing regimens produced rapid hematologic response in the great majority of pts, with and an high rate of organ response. Bortezomib represents a major advance in the clinical management of this disease.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.