SUBCUTANEOUS DARATUMUMAB + CYCLOPHOSPHAMIDE, BORTEZOMIB, AND DEXAMETHASONE (CYBORD) IN PATIENTS WITH NEWLY DIAGNOSED AMYLOID LIGHT CHAIN (AL) AMYLOIDOSIS: UPDATED SAFETY RUN-IN RESULTS OF ANDROMEDA
Author(s): ,
Raymond L. Comenzo
Affiliations:
Division of Hematology/Oncology, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center,Boston, MA,United States
,
Efstathios Kastritis
Affiliations:
Univ. of Athens School of Medicine, Alexandra General Hospital,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:
Department of Hematology, UMC Utrecht,Utrecht,Netherlands
,
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
,
Johan Aschan
Affiliations:
Janssen Research & Development,Solna,Sweden
,
Jessica Vermeulen
Affiliations:
Janssen Research & Development,Leiden,Netherlands
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
EHA Library. L. Comenzo R. Jun 15, 2019; 267458; S875
Raymond L. Comenzo
Raymond L. Comenzo
Contributions
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Abstract

Abstract: S875

Type: Oral Presentation

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

Location: Auditorium

Background
The achievement of deep and sustained hematologic response in AL amyloidosis is needed to improve organ function and overall survival. Daratumumab-based combinations have resulted in deep responses and minimal additional toxicity in multiple myeloma, making such combinations potentially ideal in the treatment of AL amyloidosis.

Aims
We present the 1-year follow up on safety and efficacy data for the 28 patients enrolled in the safety run-in cohort of ANDROMEDA (NCT03201965), a phase 3 study investigating subcutaneous DARA + CyBorD in patients with newly diagnosed AL amyloidosis.

Methods
Eligible patients had ≥1 involved organs, Eastern Cooperative Oncology Group (ECOG) score ≤2, estimated glomerular filtration rate ≥20 mL/min/1.73m2, and NT-ProBNP ≤8,500 ng/L. In the safety run-in, patients received DARA (1,800 mg in 15 mL) co-formulated with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.) administered subcutaneously (SC) qw Cycles 1-2, q2w Cycles 3-6, and q4w thereafter for ≤2 y. Cy 300 mg/m2 PO or IV, Bor 1.3 mg/m2 SC, and D 40 mg were administered qw ≤6 cycles. Hematologic response evaluations (per international amyloidosis consensus criteria, Comenzo Leukemia 2012) were q4w cycles 1-6 and every other month thereafter.

Results
Patients (N = 28) had a median (range) age of 68 (35-83) years and a median of 2 (1-4) involved organs. Heart and kidney involvement affected 54% and 61% of patients, respectively; 21% were Mayo cardiac stage IIIA at screening. Median (range) follow-up was 341 (17-449) days. Median treatment duration was 11 (0.2-14) months. Patients received a median of 11 (1-16) treatment cycles; 79% received DARA SC maintenance (>6 cycles). The overall hematologic response rate was 96% and the rate of very good partial response (VGPR) or better was 82%; 10 (36%) patients achieved CR. An additional 5 (18%) patients achieved CR based on normalization of involved free light chain (iFLC) level and negative serum and urine immunofixation, but due to suppression of uninvolved FLC (uFLC) below the lower limit of normal did not normalize the FLC ratio and thus could not be formally classified as CR. Median time to first response was 23 days, and median time to CR and VGPR were 85 (29-226) and 22 (7-228) days, respectively. At the time of data cutoff (median follow-up 341 days), one patient (with no response to treatment) experienced disease progression. All of the 10 patients achieving CR and the 5 patients with normalized iFLC level and negative serum and urine immunofixation without normalized FLC ratio continue to respond to treatment. Median duration of CR was not reached. Six patients received subsequent autologous stem cell transplant (ASCT). Four patients have died (2 due to disease progression and 2 due to events following ASCT). The most common treatment emergent adverse events included diarrhea (64%), fatigue and peripheral edema (50% each). Two patients (7%) experienced infusion related reactions, all of which were grade 1.

Conclusion
DARA-CyBorD provides high overall hematologic response and CR rate in patients with newly diagnosed AL amyloidosis with a well-tolerated safety profile. Enrollment into the randomized portion of ANDROMEDA is ongoing. 

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

Keyword(s): Amyloidosis, Free light chain, Monoclonal antibody

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