Efficacy of Bortezomib/Cyclophosphamide/Dexamethasone (VCD) Chemotherapy In Naive Patients with High Risk Cardiac Light Chain Amyloidosis (Mayo Clinic stage III)
Authors: Jaccard Arnaud , Roussel Murielle , Banos Anne , Lavergne David , Ninet Jacques , Arnulf Bertrand , Bordessoule Dominique , Bridoux Frank , Fermand Jean Paul 
Published: October 2019

Abstract
Abstract 5126

Purpose:
Severe cardiac involvement is known to confer a poor prognosis in patients with AL amyloidosis. High-dose chemotherapy is not an option for these patients and melphalan/dexamethasone (M-Dex) therapy is not able to overcome this poor prognosis (Dietrich et al, 2010). Bortezomib (Bb) is known to induce rapid hematological response in amyloidosis and its association with cyclophosphamide and dexamethasone is proven to be highly active and effective in multiple myeloma. (Reeder, Leukemia 2009). We therefore proposed to use this regimen for patients with high-risk cardiac amyloidosis as defined by Mayo Clinic stage III, treated among the French network for amyloidosis.

Patients and Method:
We retrospectively evaluated 13 patients with systemic AL amyloidosis, classified as Mayo Clinic stage III cardiac amyloidosis based on their elevated cardiac biomarkers NT-proBNP and troponine-T values treated with VCD as first line treatment in 5 centres. To reduce toxicity in these frail patients Bb was administered once weekly with a usual dosage of 1.3 mg/m2 on days 1, 8, 15 and 22 in a 5 week schedule. Dexamethasone was given the day of Bb administration and the day after, 10 or 20 mg depending on patient age and performans status; cyclophosphamide, 300 mg/m2, max 500 mg, was given orally at days 1, 8 and 15. The new criteria defined at the international amyloidosis meeting in Roma in April 2010 were used to define the hematological response.

Result:
There were 7 women and 6 men, median age was 69 (55–81). Median NT-proBNP was 12325 ng/L (1036–66000) and median troponine-T was 0, 11 mg/mL (0.04–0.61). The median number of involved organ was 2 (1–5). Median difference between pathologic and normal FLC (dFLC) was 281 mg/L (82–2976). Height patients had a renal involvement.
Median follow up of the entire cohort is 3.0 months (0–8), only 1 patients died, during ongoing VCD, probably from cardiac arrest. Median number of cycle was 3 (1–6). Height patients had a free light chain (FLC) measurement after 1 to 3 cycles (median 3) and all achieved an hematological response (4 CRs (50%), 3 PRs (37.5 %) and 1 VGPR (12.5 %) defined as a dFLC below 40 mg. The median dFLC of these 8 pts was 278 (137–3759) at diagnosis and 17.9 (0.6–298) at evaluation.
We observed non-hematological toxicity in 5 patients, sepsis in 1, non fatal cardiac decompensation in 2, diarrhoea in 1 and bowel obstruction in 1. No neuropathy or hematological toxicity was observed. Therapy was stopped before the planned 6 – 8 cycles in 2 patients due to patient choice in 1 case and to clinician choice in 1 patient in CR. Therapy is still ongoing in 8 patients.

Conclusion:
The retrospective nature, small sample size and short follow-up limit this study (which should be updated for the meeting), but the impressive hematological response rate (CR-VGPR = 62.5%) obtained very rapidly, the low toxicity profile and the excellent OS with only 1 death in these very severe cohort of naive patients with Mayo stage III (median OS 3.5 months, Dispenzieri et al, 2004) already justify a prospective phase II trial using this regimen in Mayo stage III pts.

Disclosures:
Jaccard: Janssen: Honoraria, Research Funding.