AN EARLY, WITHIN THE FIRST MONTH, AND DEEP RESPONSE, SHOULD BE THE GOAL OF THERAPY IN AL AMYLOIDOSIS
Author(s): ,
Efstathios Kastritis
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Eleni A Karatrasoglou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Ioanna Dialoupi
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Maria Gavriatopoulou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Maria Roussou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Despoina Fotiou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Nikolaos Kanellias
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Ioannis Ntanasis-Stathopoulos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Evangelos Eleutherakis-Papaiakovou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Efstathios Manios
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Magdalini Migkou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Aristea-Maria Papanota
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Elektra Papadopoulou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Kimon Stamatelopoulos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Argyrios Ntalianis
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Asimina Papanikolaou
Affiliations:
Department of Haemopathology,Evangelismos Hospital,Athens,Greece
,
Erasmia Psimenou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Charikleia Gakiopoulou
Affiliations:
1st Department of Pathology,National and Kapodistrian University of Athens,Athens,Greece
,
Ourania Tsitsilonis
Affiliations:
Department of Biology,National and Kapodistrian University of Athens,Athens,Greece
,
Maria Eirini Tselegkidi
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Ioannis Trougakos
Affiliations:
Department of Biology,National and Kapodistrian University of Athens,Athens,Greece
,
Ioannis V Kostopoulos
Affiliations:
Department of Biology,National and Kapodistrian University of Athens,Athens,Greece
,
Evangelos Terpos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
Meletios A. Dimopoulos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
EHA Library. Kastritis E. Jun 15, 2019; 266995; PS1378
Dr. Efstathios Kastritis
Dr. Efstathios Kastritis
Contributions
Abstract

Abstract: PS1378

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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< 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>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 <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<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<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<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.

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.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Amyloidosis, Free light chain, Prognosis

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