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1409 Subcutaneous Daratumumab (DARA SC) + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Asian Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: Subgroup Analysis from the Phase 3 Andromeda Study

Program: Oral and Poster Abstracts
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
multiple myeloma, Biological, antibodies, Adult, Therapies, Plasma Cell Disorders, Study Population
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Kenshi Suzuki, MD, PhD1, Ashutosh D. Wechalekar2*, Kihyun Kim, MD3*, Chihiro Shimazaki, MD, PhD4, Jin Seok Kim, MD, PhD5*, Takayuki Ikezoe, MD, PhD6, Chang-Ki Min, M.D., Ph.D.7*, Fude Zhou8*, Shinsuke Iida, MD, PhD9, Nagaaki Katoh10*, Tomoaki Fujisaki, MD11*, Ho-Jin Shin12*, NamPhuong Tran, MD13*, Xiang Qin, MD, PhD14*, Sandra Y. Vasey, MSc14*, Brenda Tromp, MSc15, Brendan M. Weiss, MD14*, Jessica Vermeulen, MD, PhD15*, Raymond L. Comenzo, MD16, Efstathios Kastritis, MD17* and Jin Lu18

1Japanese Red Cross Medical Center, Department of Hematology, Tokyo, Japan
2University College London and the Royal Free London NHS Foundation Trust, Division of Medicine, Faculty of Medical Sciences, London, United Kingdom
3Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)
4JCHO Kyoto Kuramaguchi Medical Center, Department of Hematology, Kyoto, Japan
5Yonsei University College of Medicine, Severance Hospital, Seoul, Korea, Republic of (South)
6Department of Hematology, Fukushima Medical School, Fukushima, Japan
7Seoul St. Mary’s Hospital, Seoul, Korea, Republic of (South)
8Peking University First Hospital, Renal Division, Department of Medicine, Beijing, China
9Department of Hematology and Oncology, Nagoya City University Institute of Medical and Pharmaceutical Sciences, Nagoya, Japan
10Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Nagano, Japan
11Matsuyama Red Cross Hospital, Matsuyama, Japan
12Department of Internal Medicine, Pusan National University Hospital, Busan, Korea, Republic of (South)
13Janssen Research & Development, LLC, Los Angeles, CA
14Janssen Research & Development, LLC, Spring House, PA
15Janssen Biologics B.V., Leiden, Netherlands
16Division of Hematology/Oncology, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA
17Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
18Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Collaborative Innovation Center of Hematology, Beijing, China

Introduction: Systemic AL amyloidosis is a rare disorder of clonal CD38+ plasma cells characterized by deposition of insoluble amyloid fibrils leading to tissue damage and organ dysfunction. Currently, there are no health authority-approved treatments for AL amyloidosis, and standard of care (SoC) includes therapies developed for multiple myeloma (MM). DARA is a human CD38-targeting antibody for MM. Combining DARA with VCd improved outcomes for AL amyloidosis versus VCd alone in the phase 3 ANDROMEDA study. Here, we report a subgroup analysis of Asian patients (China, Japan, and Korea) from ANDROMEDA.

Methods: Eligible patients had newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage (Mayo 2004) I-IIIA, eGFR ≥20 mL/min, and no symptomatic MM. Patients were randomized 1:1 to receive DARA SC plus VCd (D-VCd) or VCd. All patients received bortezomib (1.3 mg/m2 SC QW), cyclophosphamide (300 mg/m2 PO or IV QW), and dexamethasone (40 mg PO or IV QW) for six 28-day cycles with or without DARA SC (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20]; ENHANZE® drug delivery technology, Halozyme, Inc.) by injection QW in Cycles 1-2, Q2W in Cycles 3-6; after Cycle 6, patients continued DARA monotherapy as maintenance for up to 24 cycles (28-day cycles). Disease status was evaluated Q4W in Cycles 1-6 and Q8W after Cycle 7 until hematologic progression or major organ deterioration. The primary endpoint was overall hematologic complete response (CR) rate; key secondary endpoints included major organ deterioration progression-free survival (MOD-PFS), survival, and safety. MOD-PFS was defined as the time from randomization to any of the following events (whichever occurred first): death, clinical manifestation of cardiac or renal failure, or hematologic progression.

Results: Among 388 randomized patients (D-VCd, n=195; VCd, n=193), 60 were Asian (D-VCd, n=29; VCd, n=31). Baseline characteristics were well balanced between arms and consistent with the intent-to-treat population. The median age was 66 years, 70% and 58% had heart and kidney involvement, respectively, and 60% had ≥2 organs involved. Cardiac stage I, II and IIIA/B were 28%, 28%, and 43%, respectively. The median duration of treatment was 9.2 mo for D-VCd and 5.3 mo for VCd. Median follow-up was 9.4 mo. The overall hematologic CR rate was 59% for D-VCd and 10% for VCd (odds ratio, 13.2; 95% CI, 3.3-53.7; P<0.0001). D-VCd vs VCd achieved higher rates of very good partial response or better (≥VGPR; 93% vs 61%). MOD-PFS favored D-VCd-treated patients (HR 0.21; 95% CI, 0.06-0.75, P=0.0079). A total of 12 deaths occurred (D-VCd, n=3; VCd, n=9). The most common (≥10%) grade 3/4 TEAEs were lymphopenia (D-VCd 35%/VCd 32%), neutropenia (10%/3%), diarrhea (10%/7%), pneumonia (7%/10%), cardiac failure (7%/10%), hypokalemia (7%/10%), anemia (3%/10%), thrombocytopenia (3%/10%), hypoalbuminemia (3%/10%), and syncope (3%/10%). TEAEs leading to treatment discontinuation occurred in 1 patient in each treatment arm.

Conclusion: The addition of DARA SC to VCd was superior to VCd alone in Asian patients, resulting in deeper hematologic responses and improved clinical outcomes, including MOD-PFS, with a safety profile consistent with the overall study population. These data support the use of D-VCd in Asian patients with newly diagnosed AL amyloidosis.

Disclosures: Suzuki: Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Takeda, Amgen, Janssen and Celgene: Consultancy; Bristol-Myers Squibb, Celgene and Amgen: Research Funding. Wechalekar: Janssen, Takeda, Caelum, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim: BMS, Takeda, Amgen, Celgene, Janssen: Consultancy, Honoraria, Research Funding. Kim: Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Zhou: Peking University First Hospital: Current Employment. Iida: Celgene: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Chugai: Research Funding; Kyowa Kirin: Research Funding; AbbVie: Research Funding; Merck Sharpe Dohme: Research Funding; Janssen: Honoraria, Research Funding. Tran: Janssen: Current Employment, Current equity holder in publicly-traded company. Qin: Janssen: Current Employment. Vasey: Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss: Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Comenzo: Caleum: Consultancy; Unum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding. Kastritis: Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel/accommodations/expenses; Janssen: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel/accommodations/expenses.

OffLabel Disclosure: To evaluate the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with AL amyloidosis.

*signifies non-member of ASH