Sequential Brentuximab Vedotin and AVD in Older Patients With Newly Diagnosed Hodgkin Lymphoma
In a phase II study reported in the Journal of Clinical Oncology, Evens et al found that a regimen of brentuximab vedotin (Adcetris) given sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) was associated with good outcomes in untreated older patients with classic Hodgkin lymphoma.
The multicenter study included 48 patients with newly diagnosed disease aged ≥ 60 years enrolled between August 2012 and August 2016. Treatment consisted of 2 lead-in doses of brentuximab vedotin at 1.8 mg/kg once every 3 weeks followed by 6 cycles of AVD and then 4 doses of brentuximab vedotin consolidation in responding patients. Response-evaluable patients were those receiving two brentuximab vedotin lead-in doses and at least two cycles of AVD.
Patients had a median age of 69 years (range = 60–88 years), 63% were male, 81% had an Eastern Cooperative Oncology Group performance status of 0 or 1, 81% had stage III or IV disease, and 60% had International Prognostic Score of 3 to 7. The median Cumulative Illness Rating Scale-Geriatric comorbidity score was 7 (52% grade 3 or 4), and 12% of patients had a loss of instrumental activities of daily living at diagnosis.
Treatment Responses
Overall, 37 patients (77%) completed 6 cycles of AVD and 35 (73%) received at least 1 brentuximab vedotin consolidation dose. After brentuximab vedotin lead-in doses, a response was observed in 18 (82%) of the first 22 patients (exceeding the threshold of 13 responses in the first 22 patients for continuing the study), and complete remission was observed in 8 (36%).
Among 42 response-evaluable patients, a response was observed in 40 (95%) and complete remission in 38 (90%) after AVD. After brentuximab vedotin consolidation, overall response and complete remission rates were 95% and 93% among the 42 response-evaluable patients.
In an intent-to-treat analysis, the 2-year event-free, progression-free, and overall survival rates were 80%, 84%, and 93%. Progression-free survival at 2 years was 45% vs 100% (P < .001) for patients with Cumulative Illness Rating Scale-Geriatric comorbidity score ≥ 10 vs < 10 and 25% vs 94% (P < .001) for patients with baseline loss vs no loss of instrumental activities of daily living.
Adverse Events
Among all 48 patients, grade 3 or 4 adverse events occurred in 44%, with the most common including neutropenia (44%), febrile neutropenia (8%), pneumonia (6%), and diarrhea (6%). Grade ≥ 2 peripheral neuropathy occurred in 33% of patients and was reversible in most.
The investigators concluded, “Altogether, sequential [brentuximab vedotin]-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.”
The study was supported by Seattle Genetics as an investigator-initiated clinical trial.
Andrew M. Evens, DO, MSc, of Rutgers Cancer Institute of New Jersey, is the corresponding author for the Journal of Clinical Oncology article.
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