Efficacy of bortezomib based regimens in elderly patients with newly diagnosed AL amyloidosis and heart failure.

RIVA, ELOISA; AGUIRRE, MARÍA ADELA; DUARTE, PATRICIO; POSADAS-MARTÍNEZ, MARÍA LOURDES; CARRETERO, MARCELINA; RIOS, OLIDAY; GARRIDO, DAVID; BRULC, ERIKA B.; PEÑA, CAMILA; NUCIFORA, ELSA MERCEDES

HEIDELBERG

Simposio; XVIIIth International Symposium on Amyloidosis; 2022

Contribution ID : 363Track / Type : ISA 2022 Abstract SubmissionFormat : Poster PresentationTitle : Efficacy of bortezomib based regimens in elderly patients with newly diagnosed AL amyloidosis and heart failure.Author(s) : Garrido, David; Posadas, Maria Lourdes; Riva, Eloisa; Brulc, Erika; Carretero, Marcelina; Aguirre, Adela; Peña, Camila; Ríos, Oliday; Duarte, Patricio; Martínez, Lina; Enciso, Leonardo; Fernández, Julio; von Glassenap, Alana; Nucifora, Elsa; Ruiz-Argüelles, Guillermo JoseBackground: Immunoglobulin light chain amyloidosis (AL amyloidosis) is a monoclonal gammopathy characterized by the systemic deposition of amyloid fibrils derived from the immunoglobulin light chains or its fragment in peripheral tissues affecting predominantly kidneys and heart 1. The use of Bortezomib during induction therapy followed by consolidation with high dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) has become the standard therapy in fit younger patients fulfilling strict eligibility criteria 2. The goal of the AL amyloidosis treatment is to eradicate the amyloidogenic clone, obtain the organ function recovery, and in elderly patients the thorough control of adverse events related to therapy plays a major role 3. In this context, the use of triplet regimens with bortezomib backbone may appear to be efficacious and well tolerated 4.Objective: Estimate overall survival and response of bortezomib based regimenes (BBR) in patients with age ≥65 years with newly diagnosed AL amyloidosis and heart failure, and compare it with non-BBRMaterial & Methods: Retrospective cohort study including patients aged ≥65 years with newly diagnosed AL amyloidosis and receiving bortezomib based regimenes (BBR) as induction therapy, without consolidative therapy with auto-HSCT, and presenting heart failure at diagnosis. The analysis was based on the Grupo de Estudio Latinoamericano de Mieloma Múltiple (GELAMM) registry, from January 2009 to December 2019 in centers from Uruguay, Chile, Argentina, Cuba, Colombia, México, and Paraguay. The primary outcomes evaluated included five year overall survival (OS), and response rate. Proportions were compared with Fisher exact test Survival analysis was performed using the Kaplan-Meier method and Log-Rank test. Results: thirty five patients were included with a median age of 73 years (IQR 8.0), and 68.6% males (24/35). The frequency of lambda chain AL amyloidosis was 75% (24/32). Regarding clinical manifestations at diagnosis, nephrotic syndrome was registered in 53.1% (17/32), macroglossia 50% (16/32), purpuric lesions 65% (13/20), hepatomegaly 38.2% (13/34), asthenia 75% (15/20), weight loss 47.1% (16/34), polyneuropathy 46.9% (15/32), disauthonomy 61.8% (21/34), gastrointestinal symptoms 44.1% (15/34), and cutaneous manifestations 29.4% (10/34). The majority of patients received BBR (57.1%, 16/28), with VCD being the most frequent (15/16), and only one patient on VMP. The overall response rate (ORR) with BBR was 83.3% (10/12), significantly higher than the ORR achieved with non-BBR 33.3% (3/9)(p=0.03). Also, BBR achieved very good partial response or better in 41.2%.(5/12),The 7-year OS for the whole cohort was 13.6% (95% CI 5% to 41%). In patients receiving BBR the 7-year OS was 23.4% (95% CI 8% to 61.9%) whereas in the non-BBR the 7-year OS was 14.3% (95% CI 3% to 76.4%). The median survival in the BBR group was 26 months, and the median survival in patients not receiving BBR was 13 months (Log-Rank, p=0.46).Summary & Conclusion: In elderly patients with newly diagnosed AL amyloidosis and heart failure, the use of BBR during induction tends to achieve a higher median survival and survival rate at 7 years. However, the reduced number of patients included does not allow us to establish conclusions. More studies are required to corroborate our findings. Figure 1.: Selection of patients included in the analysis. From 35 patients included in the final analysis, induction regimen was reported in 28 of them.Figure 2.: Kaplan-Meier curve of patients aged ≥65 years with newly diagnosed AL amyloidosis and heart failure not receiving auto-HSCT as consolidation therapy.Figure 3.: Kaplan-Meier curve of patients aged ≥65 years with newly diagnosed AL amyloidosis and heart failure not receiving auto-HSCT as consolidation therapy, classified by the use of bortezomib based regimenes as induction therapy; BBR, bortezomib based regimenes (Receiving BBR=1, no receiving BBR=0).References1.Picken MM. The Pathology of Amyloidosis in Classification: A Review. Acta Haematol. 2020;143(4):322-3342.Vaxman I, Gertz M. Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis. Acta Haematol. 2019;141(2):93-1063.Nuvolone M, Milani P, Palladini G, Merlini G. Management of the elderly patient with AL amyloidosis. Eur J Intern Med. 2018;58:48-56.4.Chari A, Barley K, Jagannath S, Osman K. Safety and efficacy of tri