PS1378 AN EARLY, WITHIN THE FIRST MONTH, AND DEEP RESPONSE, SHOULD BE THE GOAL OF THERAPY IN AL AMYLOIDOSIS
Authors: E. Kastritis, E.A. Karatrasoglou, I. Dialoupi, M. Gavriatopoulou, M. Roussou, D. Fotiou, N. Kanellias, I. Ntanasis‐Stathopoulos, E. Eleutherakis‐Papaiakovou, E. Manios, M. Migkou, A.‐M. Papanota, E. Papadopoulou, K. Stamatelopoulos, A. Ntalianis, A. Papanikolaou, E. Psimenou, C. Gakiopoulou, O. Tsitsilonis, M.E. Tselegkidi, I. Trougakos, I.V. Kostopoulos, E. Terpos, M.A. Dimopoulos
Journal: HemaSphere (2019)

Background: The goal of therapy in AL amyloidosis is to reduce the burden of amyloidogenic light chains and their toxic effect of tissues and organs, especially the heart. It has been proposed that if a response has not been achieved within the first 3 months, then a change of therapy should be considered. However, even this relatively short period may be detrimental in this disease. Aims: To evaluate the importance of early response to bortezomib‐based therapy in previously untreated patients with AL amyloidosis Methods: We analyzed the outcomes of 205 consecutive patients with previously untreated AL amyloidosis with available data for evaluation of response at 28 days and at 3 months post initiation of bortezomib‐based therapy. Results: median age was 65 years, 57% were males; 69.5% had renal involvement, median eGFR was 73 ml/min/1.73 m2 and 3% required dialysis at the time of diagnosis. Heart was involved in 69%, median baseline NTproBNP was 2364 pg/ml and per Mayo stage 18%, 52.5%, 18.5% and 11% patients were stage −1, −2‐, 3A and 3B respectively. Liver was involved in 19% and peripheral/autonomic nerves in 23%. Median baseline dFLC was 194 mg/L and 13% had baseline dFLC&lt; 50 mg/L. Median follow up for living patients is 38 months and median OS is 41 months. At 1 month landmark, among patients with baseline dFLC&gt;50 mg/L, 29% had achieved at least VGPR, 27.5% a PR while 43% had not achieved a hematologic response. The respective median OS for the three groups was 57, 34 and 14 months (p = 0.026). The early death rate (i.e &lt;6 months), however, was 13%, 14% and 24% (p = 0.152) for the three early response groups. At 3 months landmark, at least VGPR rate was 46%, PR was 26% and 29% had not achieved a response and the respective median OS was 84, 29 and 20 months ( p &lt; 0.001), however, 10% of the patients died after the 1st month and before the 3rd month of therapy and 60% of them had not achieve a response at 1 month. To evaluate the impact of early response in patients at different risk, we performed an analysis by Mayo stage. In stage 1 or 2 patients VGPR, PR or NR at 1 month was associated with median OS of 112, 47 and 25 months respectively (p = 0.021). In stage 3 patients the respective OS was 79, 38 and 4 months (p = 0.021). In multivariate analysis, adjusting for baseline dFLC levels and Mayo stage, the achievement of a VGPR at 1 month was associated with a reduced risk of death (HR: 0.438, p = 0.003). At 3 month landmark, the OS in stage 1 or 2 patients for VGPR, PR or NR was 85, 47 and 21 months respectively ( p &lt; 0.001) and in stage 3 patients was 30, 12 and 6 months; in multivariate analysis, adjusting for baseline dFLC and Mayo stage, the HR for death was 0.290 ( p &lt; 0.001) for patients that had a VGPR or better vs those without a response while for those with a PR was 0.684 (p = 0.25) vs those without a response. Summary/Conclusion: the achievement of early and deep response, within the first month of therapy, should be the goal of therapy in patients with AL amyloidosis, especially those with stage 3 disease. Less than a VGPR after 3 months of therapy should prompt to change therapy. The most active combination should be used to rapidly reduce toxic FLCs, however, even among those who achieve an early VGPR, early mortality remains high, indicating the advanced cardiac dysfunction and late recognition of the disease.