ASH 2017: Addition of Brentuximab Vedotin to Multidrug Regimen Reduces Risk of First-Line Treatment Failure in Advanced Hodgkin Lymphoma
Patients with advanced Hodgkin lymphoma (HL) who were treated with a multidrug regimen that included the targeted agent brentuximab vedotin (Adcetris) had a 23% reduction in the risk of disease progression, death, or the need for additional therapy, compared with patients who received the standard four-drug first-line regimen for treating advanced HL, Connors et al reported at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 6).
In this multinational, phase III clinical trial, the addition of brentuximab vedotin to standard treatment improved patients’ chances of being cured with the first round of treatment, avoiding the need for additional, more intensive therapy. The study results represent the first successful effort in more than 30 years to improve outcomes of first-line treatment in patients with advanced HL without escalating the toxicity of the chemotherapy to unacceptable levels, said lead study author Joseph M. Connors, MD, Clinical Director of the British Columbia Cancer Agency Centre for Lymphoid Cancer in Vancouver.
Standard treatment for HL, consisting of the drugs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), has not changed since the 1970s, said Dr. Connors, adding that previous trials have failed to improve the outcomes achieved with ABVD without causing severe side effects.
“We expect ABVD to cure about three-quarters of patients—which means, of course, that one-quarter will not be cured,” he explained. “In this study, we’ve been able to significantly reduce that rate of treatment failure. If this new regimen is widely adopted, it will change first-line treatment of advanced HL.”
Brentuximab vedotin works by first attaching to the surface of HL cells, then entering the cells to deliver a toxic substance, he explained. This is the first time a drug designed to take advantage of a specific biologic characteristic of HL cells has been used in first-line treatment of the disease, Dr. Connors said.
Study Findings
In the study, 1,334 patients with previously untreated advanced HL were randomly assigned to receive either ABVD or brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), with up to 50 months’ follow-up. Treatment was deemed to have failed if patients’ lymphoma did not completely disappear or if its persistence prompted additional nonstudy treatment.
Although the experimental combination of brentuximab vedotin and AVD caused more nerve damage, episodes of fever, and neutropenia than ABVD, the nerve damage largely reversed during follow-up, and the rate of serious infections could be kept to low levels with the use of medication to encourage white blood cells to recover more quickly, according to Dr. Connors. The experimental combination of brentuximab vedotin and AVD meant patients didn’t receive bleomycin, which has been linked to lung damage and sometimes death.
“The experimental combination with [brentuximab vedotin] more frequently got rid of all of the disease, and this was achieved with acceptable levels of adverse effects,” said Dr. Connors. “Treatment with [brentuximab vedotin] was modestly more toxic, but when we added simple measures to improve patients’ blood counts, they were able to take it safely.”
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