ANDROMEDA: Daratumumab-based frontline standard-of-care in AL amyloidosis

Daratumumab added to bortezomib, cyclophosphamide, and dexamethasone (VCd) outperformed VCd alone with respect to survival outcomes in patients with previously untreated light chain (AL) amyloidosis. According to the authors, the results indicate that daratumumab is most efficacious in the frontline setting.

Dr Efstathios Kastritis (University of Athens, Greece) presented the final analysis of the phase 3 ANDROMEDA trial after a median follow-up of 5 years [1,2]. The study randomised 380 patients with newly diagnosed AL amyloidosis 1:1 to daratumumab plus VCd or to VCd alone. Previous analyses displayed that the daratumumab arm was associated with improved response rates in the population [1]. Dr Kastritis presented updated results from the study.

In the updated analysis, 59.5% of the participants in the daratumumab arm reached a haematologic complete response, compared with 19.2% of those in the control arm (OR 6.03; 95% CI 3.80–9.58; P<0.0001) [2]. Also, major-organ-deterioration progression-free survival was 60.2% in the daratumumab arm and 33.2% in the control arm (HR 0.44; 95% CI 0.31–0.63; P<0.0001). “Most importantly, we observed an overall survival [OS] benefit for participants in the daratumumab arm, with 60-month OS rates of 76.1% versus 64.7%,” emphasised Dr Kastritis (HR 0.62; 95% CI 0.42–0.90; P=0.012). “This result was achieved while over 70% of the participants in the control arm received daratumumab-based therapies as subsequent treatment, demonstrating the importance of using daratumumab in the frontline setting.” Results were consistent across prespecified subgroups, stratified by age, baseline weight, cardiac stage, renal stage, race, or cytogenetic risk.

The safety data was consistent with the known safety profiles of daratumumab and VCd. Grade 3 or 4 pneumonia (8.3% vs 4.3%) and grade 3 or 4 cardiac failure (6.2% vs 2.7%) were somewhat more common in the daratumumab arm. Finally, any-grade respiratory infections were more frequently observed among daratumumab receivers (25.9% vs 11.2%).

“Adding daratumumab to VCd improves survival for patients with newly diagnosed AL amyloidosis and reaffirms frontline daratumumab plus VCd as the standard-of-care for patients with this difficult-to-treat disease,” concluded Dr Kastritis.

1. Kastritis E, et al. N Engl J Med 2021;385(1):46-58.
2. Kastritis E, et al. Subcutaneous daratumumab + bortezomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed light-chain amyloidosis: overall survival and final major organ deterioration-progression-free survival results from the phase 3 ANDROMEDA study. Abstract 891, 66^th ASH Annual Meeting, 7–10 December 2024, San Diego, CA, USA.

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Posted on 29 January 202529 January 2025