UPDATED RESULTS FROM PHASE 3 ANDROMEDA STUDY OF PATIENTS WITH NEWLY DIAGNOSED LIGHT CHAIN AMYLOIDOSIS TREATED WITH BORTEZOMIB, CYCLOPHOSPHAMIDE, AND DEXAMETHASONE PLUS SUBCUTANEOUS DARATUMUMAB
Author(s): ,
Efstathios Kastritis
Affiliations:
National and Kapodistrian University of Athens,Athens,Greece
,
Vaishali Sanchorawala
Affiliations:
Boston University School of Medicine and Boston Medical Center,Boston,United States
,
Giovanni Palladini
Affiliations:
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia,Pavia,Italy
,
Monique Minnema
Affiliations:
University Medical Center Utrecht,Utrecht,Netherlands
,
Ashutosh Wechalekar
Affiliations:
University College London,London,United Kingdom
,
Arnaud Jaccard
Affiliations:
Centre Hospitalier Universitaire and Reference Center for AL Amyloidosis,Limoges,France
,
Angela Dispenzieri
Affiliations:
Mayo Clinic,Rochester,United States
,
Hans Lee
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Divaya Bhutani
Affiliations:
Columbia University Medical Center,New York,United States
,
Simon Gibbs
Affiliations:
Monash University Eastern Health Clinical School,Melbourne,Australia
,
Peter Mollee
Affiliations:
Princess Alexandra Hospital and University of Queensland Medical School,Brisbane,Australia
,
Christopher Venner
Affiliations:
Cross Cancer Institute, University of Alberta,Edmonton,Canada
,
Jin Lu
Affiliations:
Peking University People’s Hospital, Peking University Institute of Hematology,Beijing,China
,
Stefan Schönland
Affiliations:
Amyloidosis Center, Heidelberg University Hospital,Heidelberg,Germany
,
Moshe Gatt
Affiliations:
Hadassah Hebrew University Medical Center,Jerusalem,Israel
,
Kenshi Suzuki
Affiliations:
Japanese Red Cross Medical Center,Tokyo,Japan
,
Kihyun Kim
Affiliations:
Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Korea, Democratic People's Republic Of
,
Teresa Cibeira
Affiliations:
Hospital Clinic of Barcelona,Barcelona,Spain
,
Meral Beksac
Affiliations:
Ankara University,Ankara,Turkey
,
Edward Libby
Affiliations:
University of Washington,Seattle,United States
,
Jason Valent
Affiliations:
Taussig Cancer Center, Cleveland Clinic,Cleveland,United States
,
Vania Hungria
Affiliations:
Clinica Sao Germano,Sao Paulo,Brazil
,
Sandy Wong
Affiliations:
University of California San Francisco,San Francisco,United States
,
Michael Rosenzweig
Affiliations:
Judy and Bernard Briskin Center for Multiple Myeloma Research,Duarte,United States
,
Naresh Bumma
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Dominique Chauveau
Affiliations:
CHU de Toulouse-Hôpital Rangueil,Toulouse,France
,
NamPhuong Tran
Affiliations:
Janssen Research & Development, LLC,Los Angeles,United States
,
Xiang Qin
Affiliations:
Janssen Research & Development, LLC,Spring House,United States
,
Sandra Vasey
Affiliations:
Janssen Research & Development, LLC,Spring House,United States
,
Brenda Tromp
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Brendan Weiss
Affiliations:
Janssen Research & Development, LLC,Spring House,United States
,
Jessica Vermeulen
Affiliations:
Janssen Research & Development, LLC,Leiden,Netherlands
,
Raymond Comenzo
Affiliations:
John C. Davis Myeloma and Amyloid Program, Tufts Medical Center,Boston,United States
Giampaolo Merlini
Affiliations:
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia,Pavia,Italy
EHA Library. KASTRITIS E. 06/09/21; 324597; S189
Dr. EFSTATHIOS KASTRITIS
Dr. EFSTATHIOS KASTRITIS
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S189

Type: Oral Presentation

Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis

Background
Light chain amyloidosis (AL) is a systemic plasma cell disease where organ impairment and death can occur due to insoluble amyloid fibrils deposition. Adding subcutaneous daratumumab to the standard of care (bortezomib, cyclophosphamide, and dexamethasone [VCd]) in ANDROMEDA (NCT03201965) led to superior outcomes versus VCd alone (primary results), including greater hematologic complete response (CR) rates and an acceptable safety profile. In January 2021, Daratumumab+VCd was approved for patients with newly diagnosed AL amyloidosis.

Aims
To report updated primary results with longer follow up from the ANDROMEDA study.

Methods
ANDROMEDA is an ongoing open-label, randomized, active-controlled, phase 3 trial. Adult patients with newly diagnosed AL amyloidosis were randomly assigned 1:1 to receive daratumumab+VCd or VCd for six 28-day cycles. Written informed consent was obtained from all patients. Bortezomib dosed at 1.3 mg/m2, cyclophosphamide at 300 mg/m2 (up to 500 mg weekly), and dexamethasone at 40 mg were administered every week. Subcutaneous daratumumab was administered once weekly in cycles 1 and 2 and every 2 weeks in cycles 3 to 6. Patients in the daratumumab+VCd arm received only subcutaneous daratumumab after cycle 6, every 4 weeks (up to a total of 24 cycles from first dose). Disease status was assessed every 4 weeks in cycles 1 to 6 and every 8 weeks thereafter. Overall hematologic CR rate (intent-to-treat population) was the primary endpoint. Time to hematologic response, major organ deterioration progression-free survival, survival, organ response rate, and safety were the secondary endpoints.

Results
Among 388 randomized patients, 195 received daratumumab+VCd and 193 received VCd alone. At the November 2020 cutoff, the median duration of treatment for daratumumab+VCd and VCd arms was 18.5 and 5.3 months, respectively, and 78 patients (40%) in the daratumumab+VCd arm were still receiving treatment. The overall hematologic CR rate in the daratumumab+VCd arm (59%) was significantly higher versus the VCd arm (19%; odds ratio [95% CI], 5.9 [3.7–9.4]; P<0.0001). More patients achieved a very good partial response or better (≥VGPR) with daratumumab+VCd (79%) compared with VCd alone (50%; odds ratio [95% CI], 3.7 [2.4–5.9]; P<0.0001). Among patients who responded, the median time from randomization to ≥VGPR was shorter in the daratumumab+VCd arm (0.56 months) versus the VCd arm (0.82 months). Greater cardiac response rates were achieved at 6 months with daratumumab+VCd (42%) versus VCd alone (22%) and at 12 months (57% versus 28%); similarly, renal response rates were greater with daratumumab+VCd (54%) versus VCd alone (27%) at 6 months and at 12 months (57% versus 27%). Overall, 71 patients died (daratumumab+VCd, 31; VCd, 40). Starting cycle 7, no grade 3/4 treatment-emergent adverse events occurred in ≥5% of patients in the daratumumab+VCd arm. After cycle 6, no systemic administration-related reactions were reported with in the daratumumab+VCd. Major organ deterioration progression-free survival is scheduled to be updated after approximately 200 events. 

Conclusion
Updated results from the ANDROMEDA study further support that in patients with newly diagnosed AL amyloidosis, the daratumumab+VCd combination is clinically superior compared with VCd alone. Following its recent approval, the daratumumab+VCd combination represents a new standard of care for patients with AL amyloidosis.

Keyword(s): Amyloidosis

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S189

Type: Oral Presentation

Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis

Background
Light chain amyloidosis (AL) is a systemic plasma cell disease where organ impairment and death can occur due to insoluble amyloid fibrils deposition. Adding subcutaneous daratumumab to the standard of care (bortezomib, cyclophosphamide, and dexamethasone [VCd]) in ANDROMEDA (NCT03201965) led to superior outcomes versus VCd alone (primary results), including greater hematologic complete response (CR) rates and an acceptable safety profile. In January 2021, Daratumumab+VCd was approved for patients with newly diagnosed AL amyloidosis.

Aims
To report updated primary results with longer follow up from the ANDROMEDA study.

Methods
ANDROMEDA is an ongoing open-label, randomized, active-controlled, phase 3 trial. Adult patients with newly diagnosed AL amyloidosis were randomly assigned 1:1 to receive daratumumab+VCd or VCd for six 28-day cycles. Written informed consent was obtained from all patients. Bortezomib dosed at 1.3 mg/m2, cyclophosphamide at 300 mg/m2 (up to 500 mg weekly), and dexamethasone at 40 mg were administered every week. Subcutaneous daratumumab was administered once weekly in cycles 1 and 2 and every 2 weeks in cycles 3 to 6. Patients in the daratumumab+VCd arm received only subcutaneous daratumumab after cycle 6, every 4 weeks (up to a total of 24 cycles from first dose). Disease status was assessed every 4 weeks in cycles 1 to 6 and every 8 weeks thereafter. Overall hematologic CR rate (intent-to-treat population) was the primary endpoint. Time to hematologic response, major organ deterioration progression-free survival, survival, organ response rate, and safety were the secondary endpoints.

Results
Among 388 randomized patients, 195 received daratumumab+VCd and 193 received VCd alone. At the November 2020 cutoff, the median duration of treatment for daratumumab+VCd and VCd arms was 18.5 and 5.3 months, respectively, and 78 patients (40%) in the daratumumab+VCd arm were still receiving treatment. The overall hematologic CR rate in the daratumumab+VCd arm (59%) was significantly higher versus the VCd arm (19%; odds ratio [95% CI], 5.9 [3.7–9.4]; P<0.0001). More patients achieved a very good partial response or better (≥VGPR) with daratumumab+VCd (79%) compared with VCd alone (50%; odds ratio [95% CI], 3.7 [2.4–5.9]; P<0.0001). Among patients who responded, the median time from randomization to ≥VGPR was shorter in the daratumumab+VCd arm (0.56 months) versus the VCd arm (0.82 months). Greater cardiac response rates were achieved at 6 months with daratumumab+VCd (42%) versus VCd alone (22%) and at 12 months (57% versus 28%); similarly, renal response rates were greater with daratumumab+VCd (54%) versus VCd alone (27%) at 6 months and at 12 months (57% versus 27%). Overall, 71 patients died (daratumumab+VCd, 31; VCd, 40). Starting cycle 7, no grade 3/4 treatment-emergent adverse events occurred in ≥5% of patients in the daratumumab+VCd arm. After cycle 6, no systemic administration-related reactions were reported with in the daratumumab+VCd. Major organ deterioration progression-free survival is scheduled to be updated after approximately 200 events. 

Conclusion
Updated results from the ANDROMEDA study further support that in patients with newly diagnosed AL amyloidosis, the daratumumab+VCd combination is clinically superior compared with VCd alone. Following its recent approval, the daratumumab+VCd combination represents a new standard of care for patients with AL amyloidosis.

Keyword(s): Amyloidosis

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