A complete response was seen in 53% of the 195 adults randomly assigned to receive daratumumab versus 18% who received placebo after a median follow-up of 11.4 months (P<0.001).
The drug also made a significant difference in the benchmark of survival free from major organ deterioration or hematologic progression, producing a 42% reduction (P=0.02), researchers report in the New England Journal of Medicine.
"The combination of daratumumab with CyBorD is the new standard of care for newly diagnosed patients with AL amyloidosis granting unprecedented clinical benefits and making closer the goal of curing this dreadful disease," coauthor Dr. Giampaolo Merlini of Research Hospital Policlinico San Matteo in Pavia, Italy, told Reuters Health by email.
The findings are "highly relevant for people with amyloidosis caused by monoclonal light chains because it provides unprecedented complete response rate, cardiac- and renal-function improvement, and improved survival free from major organ deterioration or hematologic progression," he said.
Janssen, which sells daratumumab under the brand name Darzalex for multiple myeloma, paid for the phase-3 study, known as ANDROMEDA. The drug was given subcutaneously for a maximum of 24 cycles, starting weekly, with longer durations between cycles as the study progressed.
AL amyloidosis is a rare but potentially lethal condition where the buildup of amyloid damages the heart, kidneys, liver and nerves.
The open-label test on 388 volunteers was done at 109 sites in 22 countries; 71% had heart involvement and 59% had kidney involvement.
After six months of treatment, the cardiac response rate was 41.5% in the daratumumab group and 22.2% in the control group. The rates of cardiac progression were 2.5% and 7.7%, respectively.
The response rates when the kidney was affected were 53.0% and 23.9% respectively. Rates of renal progression were 4.3% and 11.5%.
"The median time to hematologic complete response was 60 days in the daratumumab group and 85 days in the control group," the researchers said.
"Hematologic responses were deeper and occurred more rapidly in the daratumumab group," the researchers write. "All definitions of complete response that are associated with improved overall survival showed the superiority of daratumumab."
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However, overall survival "did not differ substantially between the two groups," the researchers acknowledge. At the 18-month mark it was roughly 77% with conventional therapy and 85% with daratumumab (hazard ratio, 0.90; 95% confidence interval, 0.53 to 1.53).
The rates of grade-3 or -4 side effects were also higher among the daratumumab recipients. Lymphopenia was seen in 13.0% in the experimental group versus 10.1% among control patients.
Respective rates were 7.8% and 4.3%.for pneumonia, 6.2% and 4.8% with cardiac failure and 5.7% and 3.7% for diarrhea.
Adverse events killed 11.9% of the daratumumab recipients and 7.4% of the volunteers getting conventional treatment.
"This is a very fragile patient population that is highly sensitive to drug side effects," said Dr. Merlini, who retired in April but had been director of the Amyloidosis Research and Treatment Center at the hospital. "Daratumumab granted a high rate of complete responses and organ responses that translate to improved survival according to previous trials. For this reason, I believe that the benefits of daratumumab treatment greatly surpass the risks."
"Now that we finally have a highly effective and approved therapy for patients with AL amyloidosis," he said, "it is of paramount importance to improve our diagnostic capability and detect the disease in the early stage, before severe cardiac damage ensues. If we start therapy in the early phase of the disease, we now have a real chance for curing what was once considered an inevitably fatal disease."
Dr. Merlini and several of his coauthors report financial ties to Janssen.
SOURCE: https://bit.ly/2T1H9ud The New England Journal of Medicine, online June 30, 2021.
By Gene Emery
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