Treatment patterns and Outcomes of patients with systemic AL amyloidosis by organ involvement: a retrospective analysis of an institutional registry from Argentina

POSADAS MARTINEZ, MARIA LOURDES; ET AL

Congreso; XVII INTERNATIONAL SYMPOSIUM ON AMYLOIDOSIS (ISA); 2020

Ma Lourdes Posadas-Martínez+, María Adela Aguirre+, Patricia Sorroche+, Diego Perez de Arenaza+, FedericoVarela+, Greloni Gustavo+, Dana Kohan+, Erika Brulc+, Ana Basquiera+, Gerardo Machnicki*, MarianaFernandez*, Elsa Nucifora+Background: AL amyloidosis diagnosis is often delayed, and prognosis is poor due to advanced,multi-organ (particularly cardiac) involvement at diagnosis. Aim:  Describe treatments andoverall survival according to organ compromise in treated AL amyloidosis patients. Methods:Retrospective cohort (2010-2019) of adult patients with AL amyloidosis from Italian Hospital ofBuenos Aires - Institutional Registry of Amyloidosis (IRA - ClinicalTrials.gov#:NCT01347047). Baseline characteristics, organ involvement, laboratory and treatment data werecollected. Organ compromise was defined as clinical and/or biomarkers and/or imaging findings.All patients were followed until death or lost to follow-up and hematologic response wasevaluated. Survival rates are expressed as the % surviving at 1, 5, and 10 years by Kaplan Meiermethod. Cox regression was used to evaluate mortality according to organ involvement atdiagnosis. Results: 91 patients with AL amyloidosis were included, median age was 63 years(53-70) and 43% (29) were women with a median Charlson score of 2 (DS 1) and ECOG statusof 2 (DS 1). The median of organ involvement was 2 (1-3). Heart and kidney were affected in71% and 72% of patients, respectively; followed by gastrointestinal and neurologicalinvolvement. Median alkaline phosphatase was 90IU (64-140), NT-Pro BNP 2899 pg/dl (874-10106), serum creatinine 1.1mg/dL (0.7-2.1), kappa/lambda ratio 0.5 (0.1-2), serum free lightchains kappa 28(10-73), lambda 73(29-466), ESR 41 (21-52), kappa/lambda urine ratio 0.68(0.5-1.5),   β2 serum microglobulin 0.4 (0.3-1.9)mg/l. Sixty-nine patients received treatment outof which 6 had a heart transplant upfront and ASCT was performed on 13 (19%). The mostfrequent first line regimens were: CyBorD 76% (51) and Thalidomide-Dexamethasone/Cyclophosphamide 11% (7).  The mean of first line cycles was 5 (SD 5). Secondline was received by 26 patients with a mean of 4 cycles (SD4) - Lenalidomide/Dexamethasonefor 42% (11) and Daratumumab for 19% (5). Three patients received a third line treatment with amean of 4 cycles (SD 3). The median follow-up for treated patients was 66 months (IC 24-128).Overall hematologic best response rate (intention-to-treat) was: complete remission 46% (32),very good partial remission 7% (5), partial remission 5% (3) and no response 26% (18). Response was not evaluable in 11 patients (2 deaths, 1 discontinued treatment by patient´sdecision, 2 with insufficient follow-up time and 6 referred to other institutions). Overallmortality was 38% (26, CI 27-50). Survival was 94% (84-98) at 1 year, 75% (63-84) at 5 and61% (46-74) at 10 years. Number of organs compromised and higher levels of proBNP wereassociated with higher risk of mortality (HR1.5 and HR1, respectively). Kidney, gastrointestinaland neurological involvements were not associated with mortality. Conclusion: Number oforgans involved, and cardiac compromise were associated with poorer prognosis on this cohortof patients.