TY - JOUR
T1 - Daratumumab Plus CyBorD for Patients With Newly Diagnosed AL Amyloidosis
T2 - Safety Run-in Results of ANDROMEDA
AU - Palladini, Giovanni
AU - Kastritis, Efstathios
AU - Maurer, Mathew S
AU - Zonder, Jeffrey A
AU - Minnema, Monique C
AU - Wechalekar, Ashutosh D
AU - Jaccard, Arnaud
AU - Lee, Hans C
AU - Bumma, Naresh
AU - Kaufman, Jonathan L
AU - Medvedova, Eva
AU - Kovacsovics, Tibor J
AU - Rosenzweig, Michael A
AU - Sanchorawala, Vaishali
AU - Qin, Xiang
AU - Vasey, Sandra Y
AU - Weiss, B
AU - Vermeulen, Jessica
AU - Merlini, Giampaolo
AU - Comenzo, Raymond L
N1 - Funding Information:
The authors thank the patients who participated in the ANDROMEDA study and their families, study investigators, and staff at each of the clinical sites; staff involved in data collection and analyses; and members of the Data and Safety Monitoring Committee. This study was sponsored by Janssen Research & Development, LLC. Medical writing and editorial support were provided by Elise Blankenship and Jill E. Kolesar of MedErgy, and were funded by Janssen Global Services, LLC.
Funding Information:
The study was registered at ClinicalTrials.gov (NCT03201965), and was sponsored by Janssen Research & Development, LLC. Institutional review boards or independent ethics committees at study sites approved this study. Each patient provided written consent according to local requirements. The investigators and sponsor devised the study design and analysis. Study data were collected by investigators and their research teams. Janssen conducted the final data analysis and verified data accuracy. Investigators were not restricted by confidentiality agreements and had full accessibility to all data.
Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/7/2
Y1 - 2020/7/2
N2 - Although no therapies are approved for light chain (AL) amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is considered standard of care. Based on outcomes of daratumumab in multiple myeloma (MM), the phase 3 ANDROMEDA study (NCT03201965) is evaluating daratumumab-CyBorD vs CyBorD in newly diagnosed AL amyloidosis. We report results of the 28-patient safety run-in. Patients received subcutaneous daratumumab (DARA SC) weekly in cycles 1 to 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter for up to 2 years. CyBorD was given weekly for 6 cycles. Patients had a median of 2 involved organs (kidney, 68%; cardiac, 61%). Patients received a median of 16 (range, 1-23) treatment cycles. Treatment-emergent adverse events were consistent with DARA SC in MM and CyBorD. Infusion-related reactions occurred in 1 patient (grade 1). No grade 5 treatment-emergent adverse events occurred; 5 patients died, including 3 after transplant. Overall hematologic response rate was 96%, with a complete hematologic response in 15 (54%) patients; at least partial response occurred in 20, 22, and 17 patients at 1, 3, and 6 months, respectively. Renal response occurred in 6 of 16, 7 of 15, and 10 of 15 patients, and cardiac response occurred in 6 of 16, 6 of 13, and 8 of 13 patients at 3, 6, and 12 months, respectively. Hepatic response occurred in 2 of 3 patients at 12 months. Daratumumab-CyBorD was well tolerated, with no new safety concerns versus the intravenous formulation, and demonstrated robust hematologic and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT03201965.
AB - Although no therapies are approved for light chain (AL) amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is considered standard of care. Based on outcomes of daratumumab in multiple myeloma (MM), the phase 3 ANDROMEDA study (NCT03201965) is evaluating daratumumab-CyBorD vs CyBorD in newly diagnosed AL amyloidosis. We report results of the 28-patient safety run-in. Patients received subcutaneous daratumumab (DARA SC) weekly in cycles 1 to 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter for up to 2 years. CyBorD was given weekly for 6 cycles. Patients had a median of 2 involved organs (kidney, 68%; cardiac, 61%). Patients received a median of 16 (range, 1-23) treatment cycles. Treatment-emergent adverse events were consistent with DARA SC in MM and CyBorD. Infusion-related reactions occurred in 1 patient (grade 1). No grade 5 treatment-emergent adverse events occurred; 5 patients died, including 3 after transplant. Overall hematologic response rate was 96%, with a complete hematologic response in 15 (54%) patients; at least partial response occurred in 20, 22, and 17 patients at 1, 3, and 6 months, respectively. Renal response occurred in 6 of 16, 7 of 15, and 10 of 15 patients, and cardiac response occurred in 6 of 16, 6 of 13, and 8 of 13 patients at 3, 6, and 12 months, respectively. Hepatic response occurred in 2 of 3 patients at 12 months. Daratumumab-CyBorD was well tolerated, with no new safety concerns versus the intravenous formulation, and demonstrated robust hematologic and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT03201965.
UR - http://www.scopus.com/inward/record.url?scp=85086737056&partnerID=8YFLogxK
U2 - 10.1182/blood.2019004460
DO - 10.1182/blood.2019004460
M3 - Article
C2 - 32244252
SN - 0006-4971
VL - 136
SP - 71
EP - 80
JO - Blood
JF - Blood
IS - 1
ER -