Τίτλος:
Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: Safety run-in results of ANDROMEDA
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020 by The American Society of Hematology.
Συγγραφείς:
Palladini, G.
Kastritis, E.
Maurer, M.S.
Zonder, J.
Minnema, M.C.
Wechalekar, A.D.
Jaccard, A.
Lee, H.C.
Bumma, N.
Kaufman, J.L.
Medvedova, E.
Kovacsovics, T.
Rosenzweig, M.
Sanchorawala, V.
Qin, X.
Vasey, S.Y.
Weiss, B.M.
Vermeulen, J.
Merlini, G.
Comenzo, R.L.
Περιοδικό:
Blood advances
Εκδότης:
American Society of Hematology
Λέξεις-κλειδιά:
aspartate aminotransferase; bortezomib; cyclophosphamide; daratumumab; dexamethasone; antineoplastic agent; bortezomib; cyclophosphamide; daratumumab; dexamethasone; immunoglobulin heavy chain; immunoglobulin light chain; monoclonal antibody, acute kidney failure; adult; aged; AL amyloidosis; anemia; Article; aspartate aminotransferase level; atrial fibrillation; autologous stem cell transplantation; cellulitis; chronic kidney failure; clinical article; cohort analysis; congestive heart failure; constipation; controlled study; coughing; diarrhea; dizziness; drug efficacy; drug safety; drug tolerability; dyspnea; dysuria; faintness; falling; female; heart arrhythmia; heart atrium flutter; heart palpitation; hematuria; human; hyperglycemia; hypertension; hypoalbuminemia; hypokalemia; hyponatremia; hypotension; injection site contusion; injection site erythema; insomnia; lymphocytopenia; male; multicenter study; multiple cycle treatment; nausea; nephrolithiasis; nocturia; open study; oropharynx pain; peripheral edema; peripheral neuropathy; peritonitis; phase 3 clinical trial; pneumonia; pollakisuria; priority journal; randomized controlled trial; remission; sensory neuropathy; side effect; skin discoloration; sneezing; thorax pain; thrombocytopenia; treatment duration; treatment response; upper respiratory tract infection; urinary tract pain; urine incontinence; urine retention; acute kidney failure; AL amyloidosis; blood; cellulitis; clinical trial; comparative study; follow up; middle aged; nervous system; pathology; pneumonia; treatment outcome; urine; very elderly; viscera, Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cellulitis; Cyclophosphamide; Dexamethasone; Female; Follow-Up Studies; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Nervous System; Pneumonia; Treatment Outcome; Viscera
DOI:
10.1182/BLOOD.2019004460
