Daratumumab Plus CyBorD for Patients With Newly Diagnosed AL Amyloidosis: Safety Run-in Results of ANDROMEDA.

Although no therapies are currently approved for light chain (AL) amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is considered a standard treatment for newly diagnosed patients. Based on safety and efficacy of the anti-CD38 antibody daratumumab in multiple myeloma (MM), the phase 3 ANDROMEDA study is evaluating daratumumab-CyBorD versus CyBorD in newly diagnosed AL amyloidosis. We report results of the 28-patient safety run-in. Patients received subcutaneous daratumumab (DARA SC) QW Cycles 1-2 (28 days/cycle), Q2W Cycles 3-6, and Q4W thereafter for up to 2 years. CyBorD was given weekly for 6 four-week cycles. Median age was 67.5 (range, 35-83) years; median time from diagnosis was 59.5 (range, 15-501) days. Patients had a median of 2 (range, 1-4) involved organs; kidney and cardiac involvement affected 68% and 61% of patients, respectively. Patients received a median of 16 (range, 1-23) treatment cycles. The most common any-grade treatment-emergent adverse events were diarrhea (68%), fatigue (54%), and peripheral edema (50%), consistent with DARA SC in MM and the CyBorD safety profile. Infusion-related reactions occurred in 1 patient (grade 1). No grade 5 TEAEs were reported; 5 patients died, 3 following autologous transplant. Overall hematologic response rate was 96%, with >/=very good partial response in 23 (82%) patients and complete hematologic response in 15 (54%) patients; >/=partial response occurred in 20, 22, and 17 patients at 1, 3, and 6 months, respectively. The organ response rate was 64% (median follow-up 17.6 months). Renal response occurred in 6/16, 7/15, and 10/15 patients, and cardiac response occurred in 6/16, 6/13, and 8/13 patients at 3, 6, and 12 months, respectively. Hepatic response occurred in 2/3 patients at 12 months. Daratumumab-CyBorD was well tolerated, with no new safety concerns compared with the intravenous formulation, and demonstrated robust hematologic and organ responses. http://ClinicalTrials.gov NCT03201965.