Daratumumab Combo Yields Responses in Cardiac-Involved AL Amyloidosis Trials

Daratumumab (Darzalex) plus bortezomib (Velcade), cyclophosphamide, and dexamethasone (D-VCd) produced rapid and deep hematologic responses with durable clinical benefit in Asian populations with cardiac-involved, newly diagnosed amyloid light-chain (AL) amyloidosis, according to a pooled post-hoc analysis of the phase 2 AMY2009 (NCT05250973) and phase 3 AMY3001 trials (NCT03201965) presented in a poster session at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹

What were the hematologic response outcomes?

In the Asian subgroup, the overall hematologic complete response (CR) rate was 61.0% (95% CI, 44.5%-75.8%), with 53.7% (95% CI, 37.4%-69.3%) of patients achieving a hematologic CR by month 6. The rate of hematologic very good partial response or better was 85.4%.

Among the 25 patients who achieved a hematologic CR, the median time to hematologic CR was 58 days (range, 28-240). In the China subgroup (n = 26), the overall hematologic CR rate was 65.4% (95% CI, 44.3%-82.8%), with 61.5% (95% CI, 40.6%-79.8%) achieving a hematologic CR by month 6, and a rate of hematologic very good partial response or better of 88.5%.

What were the organ response and survival outcomes?

At month 6, the cardiac response rate was 48.8% (95% CI, 32.9%-64.9%) in the Asian subgroup and 53.8% (95% CI, 33.4%-73.4%) in the China subgroup. The renal response rate at month 6 was 34.1% (95% CI, 20.1%-50.6%) in the Asian subgroup and 46.2% (95% CI, 26.6%-66.6%) in the China subgroup. The 12-month overall survival (OS) rate was 87.8% (95% CI, 78.3%-98.4%) in the Asian subgroup and 88.5% (95% CI, 77.0%-100.0%) in the China subgroup. The median OS was not reached.

What was the safety profile of D-VCd?

Among the 40 treated patients in the Asian subgroup, all experienced at least 1 treatment-emergent adverse event (TEAE), with grade 3 or higher TEAEs in 80.0% and serious TEAEs in 55.0%. TEAEs leading to death were reported in 3 patients (7.5%), and 5 deaths (12.2%) occurred overall; no patient discontinued treatment due to TEAEs. Cardiac TEAEs occurred in 30.0% of patients, most commonly cardiac failure (20.0%), with grade 3 or higher cardiac TEAEs and serious cardiac TEAEs each occurring in 17.5% of patients. The investigators reported that the safety profile of D-VCd in Asian patients was generally consistent with the overall safety population.

“D-VCd delivered rapid, deep response and durable clinical benefit alongside a manageable safety profile in Asian patients with cardiac AL amyloidosis, consistent with the findings from the individual AMY2009 and AMY3001 studies,” lead study investigator Jin Lu, from Peking University People’s Hospital of Peking University Institute of Hematology at National Clinical Research Centre for Hematologic Disease, Collaborative Innovation Center of Hematology in Beijing, China, wrote with coauthors in the poster.¹“These findings support D-VCd as an effective frontline standard of care for patients with cardiac-involved [newly diagnosed] AL amyloidosis.”

What was the analysis design and population?

The post-hoc analysis pooled cardiac-involved Asian patients from China, Japan, and Korea with newly diagnosed AL amyloidosis and cardiac stage II to IIIa disease per European modification of the Mayo Clinic cardiac staging system who were treated with D-VCd in the phase 2 AMY2009 and phase 3 AMY3001 trials. The pooled population consisted of an Asian subgroup of 41 patients, including 26 Chinese patients, with a consistent median follow-up of 11.5 months. At baseline, the median age was 61 years (range, 37-82); 65.9% of patients were male, cardiac stage II and IIIa disease were nearly equally represented (48.8% and 51.2%), patients had a mean of 2.1 organs involved, and 68.3% had renal involvement.

The FDA previously granted traditional approval to the daratumumab-based regimen for newly diagnosed AL amyloidosis in November 2025 based on the AMY3001 trial; D-VCd is the only approved frontline regimen for the disease.²

References

1. Lu J, Zhao MH, Wu Y, et al. Efficacy and safety of daratumumab plus VCd in newly diagnosed amyloid light-chain amyloidosis with cardiac involvement: a pooled analysis of Asian patients from AMY2009 and AMY3001. Presented at: 23rd Annual International Myeloma Society (IMS) Meeting & Exposition; September 23-26, 2026; Glasgow, Scotland. Poster PA-165.
2. FDA grants traditional approval to daratumumab and hyaluronidase-fihj for newly diagnosed light chain amyloidosis. News release. FDA. November 19, 2025. Accessed September 23, 2026. https://tinyurl.com/4zy8zbze