Эффективность и токсичность индукционной терапии у пациентов с впервые диагностированным системным AL-амилоидозом: результаты проспективного одноцентрового клинического исследования

Abstract

Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А).
 Materials & Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients.
 Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal.
 Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.