TY - JOUR
T1 - Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis
T2 - Phase 3 ANDROMEDA Trial
AU - Minnema, Monique C
AU - Dispenzieri, Angela
AU - Merlini, Giampaolo
AU - Comenzo, Raymond L
AU - Kastritis, Efstathios
AU - Wechalekar, Ashutosh D
AU - Grogan, Martha
AU - Witteles, Ronald
AU - Ruberg, Frederick L
AU - Maurer, Mathew S
AU - Tran, NamPhuong
AU - Qin, Xiang
AU - Vasey, Sandra Y
AU - Weiss, Brendan M
AU - Vermeulen, Jessica
AU - Jaccard, Arnaud
N1 - Funding Information:
The authors thank the patients who participated in this study and their families, the staff members at the study sites, the data and safety monitoring committee, and the staff members involved in data collection and analysis. Medical writing support was provided by Corey Eagan, MPH, and Linda V. Wychowski, PhD, of Eloquent Scientific Solutions and was funded by Janssen Global Services.
Publisher Copyright:
© 2022 The Authors
PY - 2022/11
Y1 - 2022/11
N2 - BACKGROUND: Patients with amyloid light chain amyloidosis and severe cardiac dysfunction have a poor prognosis. Treatment options that induce rapid and deep hematologic and organ responses, irrespective of cardiac involvement, are needed.OBJECTIVES: The aim of this study was to evaluate the impact of baseline cardiac stage on efficacy and safety outcomes in the phase 3 ANDROMEDA trial.METHODS: Rates of overall complete hematologic response and cardiac and renal response at 6 months and median major organ deterioration-progression-free survival and major organ deterioration-event-free survival were compared across cardiac stages (I, II, or IIIA) and treatments (daratumumab, bortezomib, cyclophosphamide, and dexamethasone [D-VCd] or bortezomib, cyclophosphamide, and dexamethasone [VCd]). Rates of adverse events (AEs) were summarized for patients with and without baseline cardiac involvement and by cardiac stage.RESULTS: Median follow-up duration was 15.7 months. The proportions of stage I, II, and IIIA patients were 23.2%, 40.2%, and 36.6%. Across cardiac stages, hematologic and organ response rates were higher and major organ deterioration-progression-free survival and major organ deterioration-event-free survival were longer with D-VCd than VCd. AE rates were similar between treatments and by cardiac stage; serious AE rates were higher in patients with cardiac involvement and increased with increasing cardiac stage. The incidence of cardiac events was numerically greater with D-VCd vs VCd, but the rate of grade 3 or 4 events was similar. The exposure-adjusted incidence rate for cardiac events was lower with D-VCd than VCd (median exposure 13.4 and 5.3 months, respectively).CONCLUSIONS: These findings demonstrate the efficacy of D-VCd over VCd in patients with newly diagnosed amyloid light chain amyloidosis across cardiac stages, thus supporting its use in patients with cardiac involvement. (NCT03201965).
AB - BACKGROUND: Patients with amyloid light chain amyloidosis and severe cardiac dysfunction have a poor prognosis. Treatment options that induce rapid and deep hematologic and organ responses, irrespective of cardiac involvement, are needed.OBJECTIVES: The aim of this study was to evaluate the impact of baseline cardiac stage on efficacy and safety outcomes in the phase 3 ANDROMEDA trial.METHODS: Rates of overall complete hematologic response and cardiac and renal response at 6 months and median major organ deterioration-progression-free survival and major organ deterioration-event-free survival were compared across cardiac stages (I, II, or IIIA) and treatments (daratumumab, bortezomib, cyclophosphamide, and dexamethasone [D-VCd] or bortezomib, cyclophosphamide, and dexamethasone [VCd]). Rates of adverse events (AEs) were summarized for patients with and without baseline cardiac involvement and by cardiac stage.RESULTS: Median follow-up duration was 15.7 months. The proportions of stage I, II, and IIIA patients were 23.2%, 40.2%, and 36.6%. Across cardiac stages, hematologic and organ response rates were higher and major organ deterioration-progression-free survival and major organ deterioration-event-free survival were longer with D-VCd than VCd. AE rates were similar between treatments and by cardiac stage; serious AE rates were higher in patients with cardiac involvement and increased with increasing cardiac stage. The incidence of cardiac events was numerically greater with D-VCd vs VCd, but the rate of grade 3 or 4 events was similar. The exposure-adjusted incidence rate for cardiac events was lower with D-VCd than VCd (median exposure 13.4 and 5.3 months, respectively).CONCLUSIONS: These findings demonstrate the efficacy of D-VCd over VCd in patients with newly diagnosed amyloid light chain amyloidosis across cardiac stages, thus supporting its use in patients with cardiac involvement. (NCT03201965).
KW - daratumumab
KW - Mayo staging system
UR - http://www.scopus.com/inward/record.url?scp=85141224668&partnerID=8YFLogxK
U2 - 10.1016/j.jaccao.2022.08.011
DO - 10.1016/j.jaccao.2022.08.011
M3 - Article
C2 - 36444227
SN - 2666-0873
VL - 4
SP - 474
EP - 487
JO - J AM Coll Cardiol CardioOnc
JF - J AM Coll Cardiol CardioOnc
IS - 4
ER -