Efficacy and Toxicity of Induction Therapy in Patients with Newly Diagnosed Systemic AL Amyloidosis: Results of a Prospective Single-Center Clinical Study

AUTOIMMUNE THROMBOCYTOPENIA

IG Rekhtina, VA Khyshova, MV Solov’ev, LP Mendeleeva

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Viktoriya Aleksandrovna Khyshova, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(983)413-02-00; e-mail: viktoria2102@icloud.com

For citation: Rekhtina IG, Khyshova VA, Solov’ev MV, Mendeleeva LP. Efficacy and Toxicity of Induction Therapy in Patients with Newly Diagnosed Systemic AL Amyloidosis: Results of a Prospective Single-Center Clinical Study. Clinical oncohematology. 2023;16(2):166–73. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-166-173

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.

Keywords: AL Amyloidosis, bortezomib, lenalidomide, efficacy, toxicity.

Received: October 31, 2022

Accepted: March 3, 2023

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