SUBCUTANEOUS DARATUMUMAB (DARA SC) + CYCLOPHOSPHAMIDE, BORTEZOMIB, AND DEXAMETHASONE (CYBORD) IN PATIENTS WITH NEWLY DIAGNOSED AMYLOID LIGHT CHAIN (AL) AMYLOIDOSIS: SAFETY RUN-IN RESULTS OF ANDROMEDA
Author(s): ,
Giampaolo Merlini
Affiliations:
Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia,Pavia,Italy
,
Efstathios Kastritis
Affiliations:
Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine,Athens,Greece
,
Mathew Maurer
Affiliations:
Presbyterian Hospital and Vanderbilt Clinic,New York, NY,United States
,
Jeffrey Zonder
Affiliations:
Barbara Ann Karmanos Cancer Institute,Detroit, MI,United States
,
Monique C. Minnema
Affiliations:
UMC Utrecht Cancer Center,Utrecht,Netherlands
,
Stefan Schӧnland
Affiliations:
Heidelberg Univ. Hospital,Heidelberg,Germany
,
Ashutosh Wechalekar
Affiliations:
Univ. College London and the Royal Free London NHS Foundation Trust,London,United Kingdom
,
Giovanni Palladini
Affiliations:
Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia,Pavia,Italy
,
Xiang Qin
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,United States
,
Sandra Y. Vasey
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,United States
,
Imran Khan
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ,United States
,
Jordan M. Schecter
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ,United States
Raymond L. Comenzo
Affiliations:
Division of Hematology/Oncology, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center,Boston, MA,United States
EHA Learning Center. Merlini G. Jun 16, 2018; 215618
Prof. Giampaolo Merlini
Prof. Giampaolo Merlini

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Abstract: PS1318

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background
Systemic AL amyloidosis is characterized by deposition of insoluble amyloid fibrils, which are derived from immunoglobulin light chains produced by clonal CD38+ plasma cells, into tissues and organs.

Aims
We present the safety run-in findings of DARA SC + CyBorD in patients with newly diagnosed AL amyloidosis in ANDROMEDA (NCT03201965).

Methods
Eligible patients had ≥1 involved organ, Eastern Cooperative Oncology Group (ECOG) score ≤2, absolute neutrophil count ≥1.0 × 109/L; hemoglobin ≥8.0 g/dL; platelet count ≥50 × 109/L; estimated glomerular filtration rate ≥20 mL/min/1.73m2, and NT-ProBNP ≤8,500 ng/L. In the safety run-in, patients received a concentrated co-formulation of DARA (1,800 mg in 15 mL) and recombinant human hyaluronidase enzyme (rHuPH20; 30,000 U) in a single, pre-mixed vial, given by manual SC injection qw in Cycles 1-2, q2w in Cycles 3-6, and q4w thereafter ≤2 y. Cyclophosphamide 300 mg/m2 PO or IV and bortezomib 1.3 mg/m2 SC were given on Days 1, 8, 15, 22 of each 28-day cycle for ≤6 cycles and dexamethasone 40 mg was given qw. Dosing was staggered ≥48 hours between patients to assess infusion related reactions (IRRs). Safety was evaluated after ≥10 patients received ≥1 treatment cycle.

Results
Patients (n = 15) had a median age of 63 (range 35-77) years and a median of 58 (range 15-157) days from diagnosis. Patients had a median of 1 (range 1-3) involved organ, with kidney involvement affecting 67% of patients, cardiac involvement in 33% of patients, and ≥2 organ involvement in 40% of patients. At baseline, 33%, 60%, and 7% of patients were grouped into Mayo Clinic cardiac stage I, II, and IIIa, respectively, and 93% of patients had an ECOG score of ≤1. Among the 14 patients with available data, baseline creatinine clearance was ≥60 mL/minute in 78.6% of patients and <60 mL/minute in 21.4% of patients. Patients received a median of 2 (range 1-4) treatment cycles and a median of 5 (range 1-10) DARA injections. At the cutoff, the most common (>2 patients) treatment emergent adverse events (TEAEs) were nausea (53%), diarrhea (40%), fatigue (33%), injection site erythema (27%), and constipation, headache, anemia, rash, and cough (20% each). Dyspnea and peripheral edema were reported in 1 patient (7%) and 2 patients (13%), respectively. One grade 3/4 TEAE (hypertension; unrelated to treatment) and no serious TEAEs occurred. IRRs occurred in 1 (6.7%) patients (all grade 1). Additional data will be presented at the meeting.

Conclusion
DARA-CyBorD is tolerable in patients with AL amyloidosis, with a low IRR rate and no new safety signals. The limited incidence of dyspnea and peripheral edema indicate a low risk for volume overload.

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

Keyword(s): Amyloidosis, Phase III

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