New Reference: SubQ Daratumumab with VCd for Newly Diagnosed Amyloidosis

In this phase 3 trial of newly diagnosed AL amyloidosis, adding subcutaneous daratumumab to VCd significantly improved hematologic complete response rate. The combination also improved cardiac and renal responses, major organ deterioration–progression-free survival. Overall survival was numerically improved with addition of daratumumab. Safety profiles were consistent with known effects, with manageable adverse events supporting D-VCd as the new standard of care.

Study

Randomized, open-label, phase 3 study [ANDROMEDA]

Newly diagnosed AL amyloidosis

Six cycles of VCd alone (n=193) vs VCd plus subQ daratumumab (D-VCd) followed by daratumumab maintenance x 2 yrs (n=195)

Efficacy

Hematological CR: 59.5% vs 19.2% (D-VCd vs. VCd) (OR 6.03 [3.80-9.58])

Cardiac response: 65% vs 32%

Renal response: 54% vs 27%

Median major organ deterioration–PFS: NR vs. 30.2 mos (HR 0.44 [0.31-0.63])

Overall survival: HR 0.62 [0.42-0.90]

5-yr OS: 76.1% vs 64.7% (HR: 0.82 [0.50-1.35])

Safety

Grade 3 or above AEs: Lymphopenia (13.0% vs 10.1%), pneumonia (8.3% vs 4.3%), diarrhea (6% vs 4%), cardiac failure (6.2% vs 2.7%), neutropenia (5.2% vs 2.7%), syncope (6.2% vs 6.4%), fatigue (5.2% vs 3.2%)

Peripheral sensory neuropathy grade >=2 (13.5% vs 9.6%)

Treatment discontinuation due to AEs: 5.2% vs 4.3%

Deaths due to AEs within 30 days: 11.4% vs 7.4%