Results of ANDROMEDA Show Promise for Add-on Daratumumab

In a phase 3 trial, daratumumab showed various benefits as an add-on therapy to the standard combination treatment of bortezomib, cyclophosphamide, and dexamethasone, according to new data presented at the American Society of Hematology’s 2021 Annual Meeting and Exposition.

The ANDROMEDA study was a phase 3 trial comparing bortezomib, cyclophosphamide, and dexamethasone therapy with daratumumab as an add-on therapy in patients with light chain amyloidosis.

To conduct the study, the researchers enrolled patients who had a new diagnosis of light chain amyloidosis, had measurable hematologic disease, had at least 1 involved organ, had cardiac stage 1-3A, had an estimated glomerular filtration rate of more 20 mL/min or greater, and did not have symptomatic multiple myeloma.

Participants were then randomly assigned 1:1 to receive either bortezomib, cyclophosphamide, and dexamethasone alone (n = 193) or bortezomib, cyclophosphamide, and dexamethasone plus daratumumab (n = 195). Bortezomib, cyclophosphamide, and dexamethasone were administered weekly for 6, 28-day cycles. Daratumumab was administered subcutaneously once weekly in cycles 1 and 2 and every 2 weeks in cycles 3 to 6. After cycle 6, participants received daratumumab monotherapy every 4 weeks.

The primary endpoint was overall hematologic complete response rate. Secondary endpoints included major organ deterioration progression-free survival, organ response rate, time to hematologic response, overall survival, and safety.

Results showed that daratumumab improved the deep hematological response rates and significantly improved hematologic complete response rates (59.5% vs 19.2%). Participants taking daratumumab also had better cardiac and renal responses after 18 months of follow-up compared with the participants taking bortezomib, cyclophosphamide, and dexamethasone alone.

Moreover, daratumumab increased the number of participants who achieved a very good partial response or better (79.0% vs 50.3%), and the median time from randomization to achieving a very good partial response or better was shorter amongst patients taking daratumumab.

“These results demonstrate the sustained clinical benefits of D-VCd vs VCd in terms of hematologic and organ responses with longer follow-up, although it should be noted that many patients in the D-VCd arm received daratumumab monotherapy following 6 cycles of D-VCd, while patients in the VCd group stopped study treatment,” the researchers noted. “Nevertheless, the study continues to support the use of D-VCd over VCd alone in patients with newly diagnosed AL amyloidosis. Following its recent approval, D-VCd represents a new SOC for patients with AL amyloidosis.”

—Amanda Balbi

Reference

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. Paper presented at: American Society of Hematology’s 2021 Annual Meeting and Exposition; December 11-14, 2021; Virtual. https://ash.confex.com/ash/2021/webprogram/Paper146820.html