Περίληψη:
Background Systemic immunoglobulin light-chain (AL) amyloidosis is
characterized by deposition of amyloid fibrils of light chains produced
by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting
antibody, may improve outcomes for this disease. Methods We randomly
assigned patients with newly diagnosed AL amyloidosis to receive six
cycles of bortezomib, cyclophosphamide, and dexamethasone either alone
(control group) or with subcutaneous daratumumab followed by
single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab
group). The primary end point was a hematologic complete response.
Results A total of 388 patients underwent randomization. The median
follow-up was 11.4 months. The percentage of patients who had a
hematologic complete response was significantly higher in the
daratumumab group than in the control group (53.3% vs. 18.1%)
(relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1;
P<0.001). Survival free from major organ deterioration or hematologic
progression favored the daratumumab group (hazard ratio for major organ
deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to
0.93; P=0.02). At 6 months, more cardiac and renal responses occurred in
the daratumumab group than in the control group (41.5% vs. 22.2% and
53.0% vs. 23.9%, respectively). The four most common grade 3 or 4
adverse events were lymphopenia (13.0% in the daratumumab group and
10.1% in the control group), pneumonia (7.8% and 4.3%, respectively),
cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%).
Systemic administration-related reactions to daratumumab occurred in
7.3% of the patients. A total of 56 patients died (27 in the
daratumumab group and 29 in the control group), most due to
amyloidosis-related cardiomyopathy. Conclusions Among patients with
newly diagnosed AL amyloidosis, the addition of daratumumab to
bortezomib, cyclophosphamide, and dexamethasone was associated with
higher frequencies of hematologic complete response and survival free
from major organ deterioration or hematologic progression. (Funded by
Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number,
.)
Daratumumab in Light-Chain Amyloidosis In a randomized trial of
bortezomib, cyclophosphamide, and dexamethasone as compared with the
same therapy plus daratumumab, patients with light-chain amyloidosis who
received daratumumab had a higher frequency of hematologic complete
response than those who did not (53.3% vs. 18.1%). Deaths were most
commonly due to cardiac failure.
Συγγραφείς:
Kastritis, E.
Palladini, G.
Minnema, M. C.
Wechalekar, A. D.
and Jaccard, A.
Lee, H. C.
Sanchorawala, V
Gibbs, S. and
Mollee, P.
Venner, C. P.
Lu, J.
Schonland, S.
Gatt, M.
E.
Suzuki, K.
Kim, K.
Cibeira, M. T.
Beksac, M. and
Libby, E.
Valent, J.
Hungria, V
Wong, S. W.
Rosenzweig,
M.
Bumma, N.
Huart, A.
Dimopoulos, M. A.
Bhutani, D. and
Waxman, A. J.
Goodman, S. A.
Zonder, J. A.
Lam, S.
Song,
K.
Hansen, T.
Manier, S.
Roeloffzen, W.
Jamroziak, K.
and Kwok, F.
Shimazaki, C.
Kim, J-S
Crusoe, E.
Ahmadi,
T.
Tran, N. P.
Qin, X.
Vasey, S. Y.
Tromp, B. and
Schecter, J. M.
Weiss, B. M.
Zhuang, S. H.
Vermeulen, J. and
Merlini, G.
Comenzo, R. L.
ANDROMEDA Trial Investigators
