The 18-month longer follow-up results of the ANDROMEDA study demonstrated sustained clinical benefits of D-VCd versus VCd in terms of hematologic and organ responses in patients with newly diagnosed light chain amyloidosis, with no additional safety signals.
Primary analysis (6- and 12-month follow-up) of the randomized, open-label, active-controlled, phase 3 ANDROMEDA study (NCT03201965) demonstrated that the addition of subcutaneous daratumumab to bortezomib/cyclophosphamide/dexamethasone (D-VCd) was superior to VCd alone, with higher rates of hematologic complete response and an acceptable safety profile, in patients with light chain amyloidosis. Updated 18-month analysis data of the ANDROMEDA study were reported at the 2021 ASH Annual Meeting and summarized here.
This study enrolled patients with newly diagnosed light chain amyloidosis with measurable hematologic disease, ≥1 involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate ≥20 mL/min, and absence of symptomatic multiple myeloma. Eligible patients were randomized 1:1 to receive six 28-day cycles of D-VCd (subcutaneous daratumumab [1800 mg co-formulated with recombinant human hyaluronidase PH20 in 15 mL weekly in cycles 1, 2; and every 2 weeks in cycles 3-6]; bortezomib [1.3 mg/m2]; cyclophosphamide [300 mg/m2 up to 500 mg per week]; dexamethasone [20-40 mg]) or weekly VCd. Patients in the D-VCd arm received only subcutaneous daratumumab after cycle 6, every 4 weeks up to a total of 24 cycles from first dose. The primary end point was hematologic complete response rate; secondary end points included major organ deterioration–progression-free survival, organ response rate, time to hematologic response, overall survival, and safety. Data cutoff was May 2021.
A total of 388 patients were enrolled in the study. Of these, 195 patients received D-VCd and 193 patients received VCd alone. The median duration of D-VCd treatment was 21.3 months; median duration of VCd treatment was 5.3 months. In the D-VCd arm, 149 (77.2%) patients received daratumumab monotherapy after completing 6 cycles of D-VCd; of those, 17 (11.4%) are still receiving treatment.
The D-VCd treatment arm showed higher rates of deep hematologic responses and organ responses. At a median follow-up of 25.8 months, patients who received D-VCd treatment achieved a significantly higher rate of hematologic complete response than those in the VCd arm (59.5% vs 19.2%, respectively; odds ratio, 6.03; P <.0001). Similarly, a significantly higher proportion of patients in the D-VCd group achieved a very good partial response or better (79.0% vs 50.3%, respectively; odds ratio, 3.74; P <.0001) compared with the VCd arm. Among responders, the median time from randomization to very good partial response or better was shorter in the D-VCd arm than in the VCd arm (0.56 vs 0.82 months, respectively). Higher 18-month cardiac response rates (53% vs 24%, respectively) and renal response rates (58% vs 26%, respectively) were achieved with D-VCd compared with VCd, which were higher than those achieved at 6-month follow-up. With additional follow-up, no new safety signals emerged with the addition of daratumumab to VCd, grade 3/4 treatment-emergent adverse events were similar (61.7% at 25.8 months vs 61.1% at 20.3 months, respectively), and no additional infusion-related reactions were reported.
The 18-month longer follow-up results of the ANDROMEDA study demonstrated the sustained clinical benefits of D-VCd versus VCd in terms of hematologic and organ responses, which might have been confounded by the higher number of patients receiving daratumumab monotherapy in the D-VCd arm following 6 cycles of D-VCd versus no treatment in the VCd group after VCd treatment.
Source: Comenzo R, Palladini G, Kastritis E, et al. Subcutaneous daratumumab with bortezomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed light chain (AL) amyloidosis: 18-month analysis of the phase 3 ANDROMEDA study. Blood. 2021;138(suppl 1):159.