Updated Safety Run-in Results of ANDROMEDA Show Benefits of Subcutaneous Daratumumab + Cyclophosphamide/Bortezomib/Dexamethasone

There are currently no approved drugs for light chain amyloidosis (AL); however, medications used to treat multiple myeloma have been prescribed off-label, demonstrating improved outcomes. Effective treatment options are still needed. Daratumumab is a human IgGκ monoclonal antibody that directly impacts tumor growth by binding to CD38, inhibiting the growth of CD38-expressing tumor cells. It was recently approved as a subcutaneous formulation in the United States and in Europe.1 To ameliorate organ dysfunction and improve overall survival, rapid, deep, and sustained hematologic responses are required in AL.

Considering daratumumab combined with bortezomib, cyclophosphamide, and dexamethasone (VCd) to be a rational approach to treating patients with newly diagnosed AL, Raymond Comenzo, MD, at Tufts Medical Center, in Boston, MA, and colleagues investigated and then presented updated results at a median follow-up of 22.9 months for the safety run-in cohort of ANDROMEDA.2

To be included in this randomized phase 3 clinical trial, all patients had been diagnosed with AL with ≥1 organs impacted, received no prior therapy, had a difference between involved and uninvolved free light chain ≥50 mg/L or M-protein ≥0.5 g/dL, and been designated as having cardiac stage I-IIIA (European Modification of Mayo 2004). A total of 28 patients were included in the study, with a median age of 68 years. Time from diagnosis was 60 days (median), and the majority (57%) of patients were cardiac stage II. The median number of involved organs was 2, with 21 new cycles of treatment received.

Low rates of administration-related reactions were observed, occurring in only 2 (7%) patients. Treatment-emergent adverse events and deaths were evaluated, and the combined treatment of daratumumab subcutaneous (SC) plus VCd showed no new safety concerns. The causes of death were in alignment with expectations for this population. In total, 5 (18%) deaths occurred, with 3 (11%) deaths being transplant-related; 1 (4%) death was due to progressive hepatic amyloidosis, peritonitis, and renal failure; and 1 (4%) death was due to progressive cardiac and liver amyloidosis.

Hematologic response rates were evaluated and daratumumab SC in combination with VCd provided high rates of hematologic responses in patients with newly diagnosed AL. In the safety run-in (N = 28), a complete response was observed in 57% of patients, very good partial response in 25%, and partial response in 14%. Importantly, hematologic responses were deep.

At 22.9 months of follow-up, robust organ responses were seen. Cardiac responses were seen in 82% of patients, renal responses were seen in 79% of patients, and liver responses were seen in 50% of patients.3

The authors concluded that with longer follow-up (median, 22.9 months), the combination of daratumumab SC and VCd was well-tolerated among patients with newly diagnosed AL. The safety profile was consistent with that previously observed for daratumumab SC and VCd, and no new safety concerns were identified with longer follow-up. Updated efficacy findings demonstrated high rates of deep and durable responses.


  1. Genmab. Genmab announces European marketing authorization for the subcutaneous formulation of Darzalex® (daratumumab) for the treatment of patients with multiple myeloma. www.globenewswire.com/news-release/2020/06/04/2043780/0/en/Genmab-Announces-European-Marketing-Authorization-for-the-Subcutaneous-Formulation-of-DARZALEX-daratumumab-for-the-Treatment-of-Patients-with-Multiple-Myeloma.html. Accessed November 30, 2020.
  2. Comenzo RL, Kastritis E, Maurer M, et al. Subcutaneous daratumumab + cyclophosphamide/bortezomib/dexamethasone in newly diagnosed AL amyloidosis: updated safety run-in results of ANDROMEDA. Presented at: 2020 International Symposium on Amyloidosis; September 14-18, 2020. Abstract OP37.
  3. JanssenMD. AMY3001 (ANDROMEDA) study. www.janssenmd.com/darzalex-faspro/clinical-data/amyloidosis/amy3001-andromeda-study#Comenzo_2020. Accessed February 17, 2021.

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