Maintained Hematologic and Organ Responses at Two Years Following Stem Cell Transplant In Systemic Light-Chain Amyloidosis (AL) Using Short-Course Bortezomib and Dexamethasone Consolidation Therapy

We report two-year follow up results from a phase II trial in which we use bortezomib and dexamethasone (BD) as consolidation following risk-adapted SCT for patients with AL (Blood 2009;114:533a).

Patients with newly diagnosed AL involving <=2 organs were assigned to MEL 100, 140 or 200mg/m2 with SCT, based on age, renal function and cardiac involvement. Responses were assessed at 2–3 mos, 12 mos and 24 mos post-SCT. Patients with persistent clonal plasma cell disease at 2–3 mos post-SCT received consolidation with BD for up to 6 cycles (two 21-day, four 35-day cycles). Organ responses and overall survival (OS) were assessed at 12 and 24 mos post-SCT.

Thirty-seven patients were enrolled with kidney (68%), heart (43%), liver/GI (14%) and peripheral nervous system (16%) involvement. Forty-one percent had two organ-involvement. Three patients were removed from study prior to SCT due to ineligibility (N=2) or co-morbid illness (N=1); 1 patient is within 100 days of SCT. Four patients with advanced cardiac disease died within 100 days of SCT, resulting in a TRM of 12% (4/33). With a median follow-up of 29 mos, the OS at 12 mos post-SCT was 86%. At 12 and 24 mos, OS in patients with cardiac involvement was 69% and 49% respectively, versus 100% at both timepoints in those without (P = 0.001). Elevations of brain natruretic peptide (BNP) and troponin-I were significantly associated with worse OS, HR 1.2 (95% CI 1.1–1.4; P = 0.001) and HR 4.2 (95% CI 1.8–9.2; P = 0.001), respectively. Post-SCT, the hematologic response rate was 55% with 24% sCR. Sixty-eight percent (19/28) received consolidation with BD for persistent clonal plasma cell disease. At 12 mos post-SCT, the hematologic response rate in evaluable patients was 95% (20/21) with 62% achieving sCR and 60% having organ improvement. At 24 mos post-SCT, the overall response rate was 82% (14/17) including 53% who maintained a sCR and 88% (15/17) who had organ improvement. Interestingly, 92% (11/12) of patients with kidney involvement had organ responses at 24 mos versus 50% (7/14) at 12 mos. Overall, 87% of patients who received BD improved their hematologic response and all patients responded after 1 cycle. There was no correlation between the number of cycles received (median 6; range 1.25–6) and response. Of the 19 patients who received post-SCT BD, 79% experienced grade III-IV toxicity, which was most often hematologic toxicity with thrombocytopenia in 41%. Grade 2 or greater peripheral neuropathy was seen in 32%.

In newly diagnosed patients with systemic AL amyloidosis, consolidation with BD following risk-adapted SCT is safe and effective for eradicating persistent clonal plasma cell disease. Hematologic responses are rapid resulting in high overall and unprecedented sCR rates. Organ function improves in the majority of patients and continues to occur over time. Cardiac involvement is associated with inferior survival and cardiac biomarkers are useful for assigning risk. Relapses are seen following completion of therapy, suggesting that a maintenance regimen following post-SCT consolidation may be worthy of further study.

Landau: Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Off Label Use: The presentation will discuss bortezomib for consolidation in AL amyloidosis. Comenzo: Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.