Compared with the standard treatment of bortezomib, cyclophosphamide, and dexamethasone (VCd), additional daratumumab (DARA) to VCd therapy demonstrated better hematological responses and clinical improvement among patients with newly diagnosed AL amyloidosis, according to phase 3 data from the ANDROMEDA study presented by Efstathios Kastritis, MD, National and Kapodistrian University of Athens, Athens, Greece at the 66^th ASH Annual Meeting in San Diego, California.

DARA-VCd has been established as the standard-of-care for newly diagnosed AL amyloidosis based on prior clinical trial results.

Researchers conducted a final analysis in a randomized, open-label, phase 3 trial to investigate major organ deterioration progression and overall survival among patients with AL amyloidosis. Major organ deterioration was defined as end-stage renal disease, end-stage cardiac disease, hematologic progression, or death.

Kastritis and colleagues concluded, “DARA-VCd significantly improves clinical outcomes for patients with newly diagnosed AL amyloidosis and reaffirms this regimen’s position as the only standard-of-care in this difficult to treat disease.”

Transcript:

Hello, my name is Efstathios Kastritis. I work in Athens, Greece, and I'm very excited to be here at ASH 2024 to present the final analysis of the ANDROMEDA study, which evaluated the addition of daratumumab to VCd in newly diagnosed patients with AL amyloidosis.

We all know that AL amyloidosis is a difficult-to-treat disease with poor outcomes for most patients. In the ANDROMEDA study, subcutaneous daratumumab was added to standard VCd and in the primary analysis a few years ago, it was shown that this resulted in substantial improvement in the complete hematologic response rate and an improvement in the major organ deterioration progression-free survival.

Here we will present the final analysis of this study after a follow-up of 5 years. In this final analysis, the complete hematologic response rate still remains substantially improved. This is confirmed. The combination also with daratumumab induces the complete hematologic response rates faster. Major organ deterioration progression-free survival in this final analysis is also substantially improved with the hazard ratio of 0.44 corresponding to a 56% reduction in the composite end point of end stage cardiac failure or renal failure, or hematologic progression, or death.

What is even more important is that in the overall survival of analysis, the addition of daratumumab to VCd was also associated with a significant improvement in the overall survival of newly diagnosed patients with AL amyloidosis, and the hazard ratio was 0.62 corresponding to a 38% reduction in the risk of death. What is very important also is that this benefit was seen despite the fact that more than 70% of the patients in the control arm, in the VCd arm, who received subsequent therapy, they received a daratumumab-based regimen.

We also confirmed in this final analysis that achieving the complete hematologic response is associated with substantial improvement in the major organ deterioration progression for survival and the overall survival. This is a very valid early end point for the valuation of anti-clonal therapies in AL amyloidosis. Regarding other responses, these were 2 to 3 times higher in the DARA-VCd-arm and especially regarding complete cardiac responses, which are defined as an [N-terminal pro-B-type natriuretic peptide] (NT-proBNP) of below 350 grams per mL, 40.7% of the patients in the DARA-VCd-arm achieved complete cardiac response versus around 13% for patients that were treated with VCd and these patients had an excellent outcome.

The safety of this combination was predictable. We didn't see any new signals and the toxicity was consistent with what we know for VCd and daratumumab.

The final analysis of the ANDROMEDA study reaffirms that daratumumab with VCd is a standard-of-care for patients with newly diagnosed amyloidosis and is the first study that shows significant overall survival improvement after comparing 2 contemporary regimens. Thank you very much.

Source:

Kastritis E, Paddadini GO, Minnema MC, et al. Subcutaneous Daratumumab (DARA) + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: Overall Survival and Final Major Organ Deterioration Progression-Free Survival Results from the Phase 3 Andromeda Study. Dec 7-10, 2024; San Diego, CA. Abstract: 891