Combination Therapy More Effective Than Standard Treatment for Rare Blood Disease

Treatment for systemic amyloid light-chain (AL) amyloidosis consisting of daratumumab (DARA) in combination with the standard treatment method, CyBorD, is more effective than CyBorD alone, according to findings presented by Mayo Clinic researchers at EHA25 Virtual, the annual meeting for the European Hematology Association (EHA).

“The addition of DARA to CyBorD was superior to CyBorD alone, resulting in deeper and more rapid hematologic responses and improved clinical outcomes with an acceptable safety profile,” said the authors.

DARA-CyBorD treatment resulted in improved major organ deterioration progression-free survival (MOD-PFS) as well as better organ responses for newly diagnosed patients with AL amyloidosis.

AL amyloidosis is a rare disease caused by an abnormal functioning of antibody-producing blood cells resulting in protein fibers made up of antibodies called light-chains. It can cause kidney, heart, liver, and nerve dysfunction and has an estimated age-adjusted incidence of 5.1 to 12.8 cases per million person-years in the United States. Without treatment, patients with AL amyloidosis can see worsening conditions leading to death within 5 years.

CyBorD is the standard-of-care treatment for AL amyloidosis and is a combination of cyclophosphamide, bortez­omib, and dexa­meth­asone.

The ANDROMEDA study featured a total of 388 patients with AL amyloidosis, 195 of which were administered both DARA and CyBorD while the other 193 were administered only CyBorD. Each patient received treatment for up to 24 cycles or until major organ deterioration, death, end of study, or withdrawal.

The complete response (CR) rate for DARA-CyBorD receivers was 53% compared with 18% for patients who received only CyBorD (odds ratio, 5.1; 95% CI, 3.2-8.2; P <.0001). Patients who received DARA-CyBorD also had higher rates for very good partial response (VGPR) or better than those who only received CyBorD (79% vs 49%).

The median time to achieve CR was 60 days for patients treated with DARA/CyBorD compared with those who received only CyBord (85 days).

Among responders, patients on the combined therapy reached VGPR or CR more quickly than those on CyBorD alone, 17 days vs 25 days.

Patients administered the DARA-CyBorD combination had higher rates of overall hematologic response compared with their counterparts who received solely CyBorD (92% vs 77%).

Patients who received DARA-CyBordD had better rates of MOD-PFT (HR, 0.58; 95% CI, 0.36-0.93, P = .0224).

Additionally, 19 of patients treated with DARA-CyBorD received subsequent treatment compared with 79 patients who received only CyBordD; 48 of those 79 patients received DARA as their subsequent treatment.

The cardiac response rate after 6 months for patients administered DARA-CyBorD was 42% compared to 22% of patients who only received CyBorD (P = .0029). Those who received DARA-CyBordD also had better renal response rates after 6 months (54% vs 27%) (P <.0001).

The most common (>5%) grade 3 or 4 treatment emergent adverse events between patients who received DARA-CyBorD verses only CyBorD were lymphopenia (13% vs 10%), pneumonia (8% vs 4%), diarrhea (6% vs 4%), congestive cardiac failure (6% vs 5%), neutropenia (5% vs 3%), syncope (5% vs 6%) and peripheral edema (3% vs 6%).

During the course of the ANDROMEDA study, a total of 56 deaths occurred; 27 were from the group administered both DARA and CyBorD and 29 were from the group administered only CyBorD.

Systemic administration-related reactions for patients who received DARA-CyBorD occurred in 14 (7%) patients. All were considered low-grade and most occurred during the first infusion.

References

Kastritis E, Palladini G, Minnema MC, et al. Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients with newly diagnosed light chain (AL) amyloidosis: Primary results from the phase 3 AMDROMEDA study. Presented at: EHA25 Virtual; June 11-21, 2020. Abstract LB2604.