Adjuvant Bortezomib and Dexamethasone Following Risk-Adapted Melphalan and Stem Cell Transplant in Systemic Light-Chain Amyloidosis (AL): A Phase II Study.
Authors: Landau Heather , Hassoun Hani , Cohen Adam D , Lesokhin Alexander , Bello Christina , Hoover Elizabeth , Riedel Elyn R , Ciminiello Jennifer , McCullagh Emily , Nimer Stephen D , Comenzo Raymond 
Published: October 2019

Abstract 533

Background:

High-dose melphalan (MEL) and autologous stem cell transplant (SCT) induces hematologic and clinical remissions in AL and results in prolonged survival. In a prior phase II study we showed that post-SCT adjuvant thalidomide and dexamethasone improved hematologic responses in 42% of patients, resulting in a 39% strictly defined complete response (sCR) rate at 12 months (mos) post-SCT (BJH 2007;139:224). With a median follow-up of 52 mos, the overall survival of patients on that study is 69%. We now report on an ongoing phase II trial in which we use adjuvant bortezomib and dexamethasone (BD) following risk-adapted SCT.

Methods:

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 adjuvant BD for up to 6 cycles (two 21-day, four 35-day cycles). At 12 mos post-SCT we evaluated hematologic, organ responses and overall survival (OS).

Results:

Thirty patients have been enrolled with kidney (63%), heart (47%), liver/GI (10%) and peripheral nervous system (10%) involvement, including 38% with two organ-involvement. Three patients were removed from study prior to SCT due to three organ-involvement, co-morbid illness or the development of pulmonary edema while receiving filgrastim for stem cell mobilization; one patient is undergoing stem cell collection. SCT-related 100-day mortality was 12% (3/26), with all deaths occurring in patients with stage II or III cardiac amyloid. With a median follow-up of 20 mos, the one-year OS post-SCT is 83%. One-year OS in patients with cardiac involvement is 50% versus 100% in those without (P < 0.01). In 23 patients evaluable post-SCT, the overall response rate was 52% with 22% sCR. Seventy-four percent (17/23) received adjuvant BD for persistent clonal plasma cell disease. One patient (4%) was ineligible for adjuvant therapy due to thrombocytopenia that developed on immunosuppressive therapy following orthotopic heart transplant. At 12 mos post-SCT, the hematologic response rate in evaluable patients was 95% (18/19) with 74% (14/19) achieving sCR and 58% (11/19) having organ improvement. Ninety-three percent (13/14) of patients who received adjuvant BD and were evaluable at 12 mos post-SCT had improved hematologic responses. Overall, of the 17 patients who received adjuvant BD, 71% of patients experienced grade II-IV toxicity with thrombocytopenia (41%), ≥ grade 2 peripheral neuropathy (35%) and respiratory infection (16%) being most common and one patient with cardiac amyloid experiencing sudden death.

Conclusions:

In newly diagnosed patients with systemic AL amyloidosis, adjuvant BD following risk-adapted SCT is well-tolerated and effective for eradicating persistent clonal plasma cell disease. At 12 mos post-SCT high overall and unprecedented sCR rates are seen with frequent organ response, demonstrating that this strategy merits further study.

Disclosures:

Comenzo: Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees.