Daratumumab for light-chain amyloidosis

The ANDROMEDA study demonstrated clear clinical benefit when adding subcutaneous (SC) daratumumab to a combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD) for patients with newly diagnosed light-chain (AL) amyloidosis.

Chemotherapy-based combinations are commonly used in AL amyloidosis, but more effective treatments are needed. Dr Efstathios Kastritis (National and Kapodistrian University of Athens, Greece) presented the phase 3 ANDROMEDA study, which evaluated subcutaneous (SC) daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-CyBorD) compared with CyBorD alone in newly diagnosed patients with AL amyloidosis [1].

In total, 388 patients with newly diagnosed AL amyloidosis were randomised to receive treatment with either CyBorD alone (n=193) or with the addition of SC daratumumab (n=195; 1,800 mg Q4W). The primary endpoint of the study was the percentage of patients who achieved a haematologic complete response.

The study met the primary endpoint; patients treated with daratumumab in combination with CyBorD had a 53.3% haematologic complete response compared to 18.1% of patients who were treated with CyBorD alone (odds ratio 5.1; 95% CI 3.2 – 8.2; P<0.0001). The six-month organ response rate was nearly doubled for patients treated with D-CyBorD versus CyBorD, for both cardiac (42% vs 22%; P=0.0029) and renal (54% vs 27%; P<0.0001) responses. The number patients surviving without disease progression was also substantially better in the arm receiving daratumumab (HR 0.58; 95% CI 0.36-0.93; P=0.02).

Overall, the safety profile of daratumumab SC in combination with CyBorD was consistent with the known safety profile of the CyBorD regimen and the known safety profile of daratumumab. The ANDROMEDA study suggests that daratumumab SC provided more rapid and deeper haematologic responses, suggesting that it may be a promising treatment for newly diagnosed patients with AL amyloidosis who are in urgent need of new treatment options.

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   1. Kastritis E, et al. Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone (CYBORD) in patients with newly diagnosed light chain (AL) amyloidosis: primary results from the phase 3 ANDROMEDA. EHA25 Virtual, 11-21 June 2020, Abstract LB2604.

 



Posted on 9 September, 202028 March, 2024