CONSOLIDATION WITH A SHORT COURSE OF DARATUMUMAB CAN SIGNIFICANTLY IMPROVE COMPLETE RESPONSE RATES IN PATIENTS WITH AL AMYLOIDOSIS OR LCDD
Author(s): ,
Efstathios Kastritis
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
,
Ioannis V Kostopoulos
Affiliations:
Department of Biology,National and Kapodistrian University of Athens,Athens,Greece
,
Ioanna Dialoupi
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
,
Nikolaos Kanellias
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
,
Evangelos Eleutherakis-Papaiakovou
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
,
Magdalini Migkou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Dimitrios C. Ziogas
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
,
Asimina Papanikolaou
Affiliations:
Department of Haemopathology,Evangelismos Hospital,Athens,Greece
,
Charikleia Gakiopoulou
Affiliations:
1st Department of Pathology,National and Kapodistrian University of Athens,Athens,Greece
,
Erasmia Psimenou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Maria Eirini Tselegkidi
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens,Athens,Greece
,
Ourania Tsitsilonis
Affiliations:
Department of Biology,National and Kapodistrian University of Athens,Athens,Greece
,
Ioannis Trougakos
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; 267009; PS1392
Dr. Efstathios Kastritis
Dr. Efstathios Kastritis
Contributions
Abstract

Abstract: PS1392

Type: Poster Presentation

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

Location: Poster area

Background

A deep hematologic response is associated with the highest probability of organ function and survival improvement in patients with AL amyloidosis.   Bortezomib-based therapy is the primary therapy for patients with AL amyloidosis but  less than 40% achieves a CR. Further improvement of hematologic response may be achieved by consolidation strategies but HDM-ASCT is associated with  significant toxicity, and only a minority of AL patients is eligible for this treatment. Recent data indicate that even a short course of daratumumab (DARA) was able to induce hematologic responses in patients with relapsed or refractory AL. Thus, DARA may be a unique treatment to improve the outcomes of patients with AL amyloidosis.

Aims

To evaluate the feasibility and activity of a short course of daratumumab as a consolidation strategy, in  patients with AL or LCDD which had achieved either PR or VGPR after completing their primary therapy, with bortezomib-based therapy.

Methods

The endpoint of this exploratory  approach was improvement of response  post completion of DARA consolidation. All patients received 4 weekly infusions of daratumumab 16 mg/kg with dexamethasone 20 mg. Pre-emptive therapy for IRR was given starting two days before the first infusion of DARA. In all patients next generation flow (NGF) according to Euroflow protocol was performed before and after consolidation

Results
26 patients (23 AL and 3 with LCDD) received DARA consolidation.  Median age is 67 and 73% were males. Kidneys and heart were involved in 80% and 73% respectively, baseline Mayo stage was 20%, 67% and 13% for stage 1,2 & 3 respectively. Baseline immunofixation in serum or urine was positive in all patients (19/23 of AL patients were lambda). Median time from start of first line therapy to DARA consolidation was 8 months and all patients had completed the planned bortezomib-based treatment.  Before consolidation all patients were in either VGPR (23/23 AL patients and 2/3 LCDD patients) or in PR (1/3 LCDD patients); all patients had positive serum and/or urine  immunofixation with or without  abnormal FLC ratio. All but one patient received the planned 4 infusion of DARA.  Mild IRR (Gr1) were observed in 3 patients. After consolidation with DARA, 42% of the patients (10/23 with AL and 1/3 with LCDD) achieved a CR. In 9/26 patients small monoclonal IgGk was observed 1 month post DARA and in all but one patient IgGk resolved at  2-3 months post DARA. The patient that received only one dose of daratumumab also achieved a CR. In all patients MRD by NGF  was positive before DARA consolidation while DARA 6/11 patients in CR became MRDnegative. All patients that did not achieve a VGPR remained MRD positive. One patient with IgGk AL that remained with positive immunofixation after DARA was MRD(neg). Because of interference with daratumumab  we repeated immunofixation, which 2 months after daratumumab became negative.  

Conclusion
Consolidation with a short course of DARA can improve the depth of response in patients with AL or LCDD that have not achieved a CR after primary therapy, including MRD negative disease in some.
 We will further explore this strategy in a formal clinical trial with a longer duration of daratumumab therapy so that CR and MRD negative rates may improve further.

 

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

Keyword(s): Amyloidosis

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