ASH 2020 | ANDROMEDA: daratumumab plus VCd in AL amyloidosis

ANDROMEDA is a clinical trial which is a randomized multicenter clinical trial of newly-diagnosed patients with AL amyloidosis who were randomized to receive daratumumab subcutaneously, along with bortezomib, cyclophosphamide, and dexamethasone or VCD, versus VCD alone in patients with newly-diagnosed AL amyloidosis. The results of this trial have been presented at the European Hematology Association meeting, and this trial has been now updated with a median follow-up of about 15 months.

This trial is showing improved primary endpoint of overall hematologic response, as well as complete hematologic response, and also organ responses with respect to cardiac response and renal response in favor of dara-VCD arm. Dara-VCD arm led to hematologic complete response in 53% of the patients compared to 18% of patients in VCD alone arm. Similarly, organ responses, specifically cardiac response, occurred in 47% of the patients with dara-VCD at 6 months compared to 27% of patients with VCD alone. And renal responses similarly occurred in 54% of patients with dara-VCD compared to 27% of patients with VCD at 6 months following treatment. In this meeting, a major organ deterioration progression-free survival, which was defined as death, hematologic progression or organ deterioration, whichever occurred first on this trial, were presented, and the major organ deterioration progression-free survival also was in favor of dara-VCD arm.

Dr. Comenzo also reported on different parameters for hematologic response criteria with respect to ISA-validated criteria of normal serum-free light chain ratio, along with immunofixation negativity as the standard criteria, as well as involved free light chain levels of less than 20 milligrams per liter. Difference between involved and uninvolved light chain of less than 10 milligrams per liter, and it showed that dara-VCD performed better than VCD with respect to hematologic response across all different criteria.

I have presented a poster at this meeting on health-related quality of life in patients who were treated on this clinical trial, and there were three patient-reported outcome tools that were used on this trial, which were SF-36, EORTC QLQ-C30 and EQ-5D-5L quality of life measures. And what was seen was that the median time to improvement was shorter and median time to worsening was longer for dara-VCD arm compared to VCD alone arm with respect to EORTC QLQ-C30 global health scale and fatigue scale, as well as EQ-5D-5L of visual analog scales, suggesting that dara-VCD can really improve and not deteriorate quality of life, even during maintenance phase.