Phase III study of subcutaneous daratumumab combination treatment shows positive response in light chain (AL) amyloidosis.- Janssen R&D

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the first randomized Phase III study investigating subcutaneous Darzalex (daratumumab) in the treatment of patients with newly diagnosed light chain (AL) amyloidosis, a rare and potentially fatal disease. The data demonstrated subcutaneous daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (D-CyBorD) resulted in a higher hematologic complete response rate (CR), (53 percent vs. 18 percent [P<0.0001]), compared to cybord. additionally, treatment with d-cybord delayed the time to major organ deterioration progression-free survival (mod-pfs), and enhanced event-free survival (mod-efs) based on mod-pfs criteria with the time to initiation of next therapy. the combination showed a safety profile consistent with subcutaneous daratumumab or cybord alone. results from the andromeda study showed that the primary endpoint, hematologic cr rate, was 53 percent for d-cybord and 18 percent for cybord (odds ratio="5.1;" 95 percent confidence interval [ci], 3.2-8.2; p><0.0001). in addition, patients receiving d-cybord achieved higher rates of overall hematologic response (92 percent vs. 77 percent) and very good partial response or better (at least vgpr; 79 percent vs. 49 percent) than patients receiving cybord. among the 195 patients who achieved at least a vgpr to treatment within the d-cybord arm, median time to at least vgpr cr was 17 60 days, compared to the 193 patients in the cybord arm whose median time to at least vgpr cr was 25 85 days. the six-month organ response rate was nearly doubled for patients treated with d-cybord versus cybord, for both cardiac (42 percent vs. 22 percent; p="0.0029)" and renal (54 percent vs. 27 percent; p><0.0001) responses. additionally, mod-pfs (hazard ratio [hr]="0.58;" 95 percent ci, 0.36-0.93, p="0.0224)" and mod-efs (hr="0.40;" 95 percent ci, 0.28-0.57, p><0.0001) favored the d-cybord arm, demonstrating substantially delayed major organ deterioration, hematologic progression or death, as well as improved event-free survival. in addition, the d-cybord arm, which is delivered subcutaneously, helped to limit intravenous fluid overload, an important treatment factor in the setting of cardiac compromised patients. the most common grade 3 4 treatment emergent adverse events occurring in more than five percent of patients for the d-cybord arm compared to the cybord arm, included lymphopenia (13 percent vs. 10 percent), pneumonia (8 percent vs. 4 percent), diarrhea (6 percent vs. 4 percent), cardiac failure (6 percent vs. 5 percent), neutropenia (5 percent vs. 3 percent), syncope (5 percent vs. 6 percent) and peripheral edema (3 percent vs. 6 percent). the study showed subcutaneous daratumumab had a low rate of administration-related reactions (arrs). systemic arrs in the d-cybord arm occurred in 14 patients (7 percent), all were grade 1-2, and most occurred during the initial administration. a total of 56 deaths occurred (d-cybord, n="27;" cybord, n="29)." the positive results are being highlighted during a press briefing at the 25th eha annual congress and will be presented during a late-breaking oral session on sunday, june 14 at 8:30 a.m. et (abstract lb2604).>