Adcetris Plus Combo Chemotherapy May Impact Survival and Response to Treatment in Subset of Patients With Hodgkin Lymphoma

Adcetris (brentuximab vedotin) with four cycles of combination chemotherapy may improve complete response rates and two-year survival in patients with early-stage, unfavorable-risk Hodgkin lymphoma, according to a study published in the Journal of Clinical Oncology.

This treatment approach may lead to a reduction or elimination of radiotherapy specifically for patients who are positron emission tomography (PET)-negative, meaning that there is no evidence of malignant disease.

“Given the limited number of patients per cohort and the nonrandomized design, the current pilot study was not designed to definitively compare the four treatment arms,” the study authors wrote. “However, the outcomes establish (four cycles of Adcetris and doxorubicin, vinblastine and dacarbazine) as a highly active and well-tolerated regimen.”

Researchers aimed to assess whether a short course of Adcetris with doxorubicin, vinblastine and dacarbazine chemotherapy can allow the safe reduction or elimination of consolidative radiation in patients with early-stage Hodgkin lymphoma. To do so, 117 patients (median age, 32 years; 50% men) ages 18 to 60 years with early-stage Hodgkin lymphoma were treated with four cycles of Adcetris and chemotherapy including doxorubicin, vinblastine and dacarbazine. Researchers assembled four different groups with different unfavorable risk factors measurements to determine bulky disease. These groups received varying doses of radiotherapy:

• Cohort 1 (30 patients): 30-Gy involved-site radiotherapy,
• Cohort 2 (29 patients): 20-Gy involved-site radiotherapy,
• Cohort 3 (29 patients): 30-Gy consolidation-volume radiotherapy and
• Cohort 4 (29 patients): no radiotherapy.

Several factors were assessed throughout the study including safety in Cohort 1 and complete response rates according to PET scans for the remaining cohorts. Follow-up was conducted for a median of 3.8 years.

The complete response rate was 93% in the group that received 30-Gy involved-site radiotherapy, 100% in those that received 20-Gy involved-site radiotherapy, 93% in patients who received 30-Gy consolidation-volume radiotherapy and 97% in those who did not received radiotherapy.

Overall progression-free survival (the time a patient lives with cancer without disease worsening) at two years for the entire patient population was 94% with overall survival (the time a patient with cancer is still alive) of 99%. At two years, progression-free survival was 93% in patients treated with 30-Gy involved-site radiotherapy, 97% in those treated with 20-Gy involved-site radiotherapy, 90% in patients treated with 30-Gy consolidation-volume radiotherapy and 97% in those who did not receive radiotherapy.

Patients experienced side effects including neutropenia (low number of white blood cells called neutrophils in the blood; 44%), febrile neutropenia (fever with neutropenia; 8%) and peripheral neuropathy (pain, numbness and weakness in the hands and feet; 54%). Side effects were largely reversible.

“The encouraging outcomes associated with short-course (Adcetris and doxorubicin, vinblastine and dacarbazine) chemotherapy alone in this study provided support for the UK RADAR study, an ongoing randomized clinical trial comparing (doxorubicin, bleomycin, vinblastine, dacarbazine) and (Adcetris and doxorubicin, vinblastine and dacarbazine) for (early-stage Hodgkin lymphoma),” the study authors wrote. “In (the) future, other novel agents including checkpoint inhibitors will be studied to enable omission of (radiotherapy) and reduce long-term toxicity in bulky (early-stage Hodgkin lymphoma).”

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