Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA

Abstract

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.

Conflict of interest statement

Conflict-of-interest disclosure: G.P. received an honorarium from Sebia, served on an advisory board for Janssen, and received a travel grant from Celgene. E.K. received honoraria from Amgen, Genesis Pharma, Janssen, Takeda, and Prothena, and received research funding from Amgen and Janssen. M.S.M. served in a consulting or advisory role for Pfizer, Akcea, Eldos, Ionis, and Prothena and received research funding from Pfizer, Eldos, and Alnylam. J.Z. served in a consulting or advisory role for Takeda, Janssen, Celgene, Bristol-Myers Squibb, Prothena, Caelum, Alnylam, and Amgen and received research support from Celgene. M.C.M. served in a consulting or advisory role for Janssen Cilag, Celgene, Servier, Gilead, and Amgen and received research funding from Celgene. A.D.W. received honoraria from Janssen, Celgene, Prothena, and Takeda; served in a consulting or advisory role for GlaxoSmithKline and Karyopharm; and received research funding from Amgen. A.J. served in a consulting or advisory role for Janssen and received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid or reimbursed by Janssen and Celgene. H.C.L. served in a consulting or advisory role for and received research funding from Amgen, Celgene, GlaxoSmithKline, Janssen, and Takeda; served in a consulting or advisory role for Sanofi; and received research funding from Daiichi Sankyo. J.L.K. consulted for AbbVie, Roche, Takeda, Janssen, and Pharmacyclics and received research funding from Amgen and Novartis. T.K. served in a consulting or advisory role for Celgene and Amgen and received research support from AbbVie, Amgen, Janssen, and Prothena. M.R. served on a speakers bureau for Janssen, Akcea, Celgene, and Takeda. V.S. served in a consulting or advisory role for Caelum and Proclara and received research funding (to institution) from Janssen, Takeda, Celgene, and Prothena. R.L.C. served in a consulting or advisory role for Janssen, Karyopharm, Takeda, Sanofi-Aventis, Caelum, and Prothena; has an immediate family member holding patents, patents pending, received royalties, participated in royalty sharing agreements, or other intellectual property interests from a discovery or technology related to health or medicine for Janssen; and received research funding from Janssen. X.Q., S.Y.V., B.M.W., and J.V. are employees of Janssen. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Swim lane plot of patients enrolled in the safety run-in portion of ANDROMEDA. Patient disposition by hematologic response is shown for the 28 patients enrolled in the safety run-in portion of the study. Black ovals indicate PR, light gray ovals indicate VGPR, and white ovals indicate CR. Dark gray rectangles indicate ASCT, and X indicates death. A, autologous stem cell transplant.

Figure 2.

Summary of overall best hematologic and organ responses. Overall best response for hematologic responses (A) and organ responses (B). Patients who met VGPR criteria and also had negative serum and urine immunofixation and normalization of iFLC, but with uFLC below the lower limit of normal (FLC ratio abnormal or normal) who therefore did not meet the criteria for CR were included in the mCR group.

Figure 3.

Reduction in dFLC levels. Lowest dFLC level achieved while on the study.