Evaluating the effectiveness of brentuximab vedotin and AVD chemotherapy combination in high-risk patients with advanced classical Hodgkin lymphoma

This study compared the long-term safety and effectiveness of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and brentuximab vedotin (Adcedris; A) + AVD (doxorubicin, vinblastine, and dacarbazine) chemotherapy combinations in high-risk patients with advanced classical Hodgkin lymphoma (cHL). The data showed that the A+AVD combination is safe and effective over the long-term for these patients. 

Classical Hodgkin lymphoma (cHL) is a cancer of white blood cells. If cancerous lymphoma cells have spread to both the upper and lower half of the body, it is known as advanced cHL. ABVD is often used to treat patients with advanced (stage III or IV) cHL. However, 25 to 30% of HL patients treated with ABVD experience relapse (worsening of the disease) or refractory (not responsive to the treatment) disease.

A + AVD is a modified version of ABVD which was shown to be more effective and safer over the long term in patients with cHL. However, it is not known if this combination continues to give better treatment results than ABVD over the long term in high-risk patients with stage IV cHL.

This study involved 1334 patients with advanced cHL. They were divided into 2 groups. Group 1 included 664 patients who received A+AVD. Group 2 included 670 patients who received ABVD. The average follow-up time was 37.1 months. Overall, 64% of patients had stage IV disease and 26% had an International Prognostic Score (IPS) of 4 to 7. The IPS is used to classify patients into risk groups. A 4-7 IPS defines a high risk of progression (high-risk disease). 

Stage IV patients who received A+AVD were 28.9% more likely to survive without cancer worsening over 3 years. After 3 years, 81.8% of the A+AVD group and 74.9% of the ABVD group had survived without cancer worsening. This benefit with A+AVD treatment was seen in both young (below 60 years) and older (over 60 years) patients. 

The estimated 2-year overall survival rate was 97.4% in the A+AVD group and 93.4% in the ABVD arm. Stage IV patients who received A+AVD were 50% more likely to survive overall than those who received ABVD.

Among patients with an IPS of 4 to 7, those who received A+AVD were 44.2% more likely to survive without cancer worsening over 3 years. After 3 years, 79.6% of the A+AVD group and 65.7% of the ABVD group had survived without cancer worsening. Among patients with an IPS of 4 to 7, those who received A+AVD were 48.1% more likely to survive overall than those who received ABVD.

96% of A+AVD and 93% of ABVD patients had treatment-related side effects. The main side effects that were more common in the A+AVD group were peripheral neuropathy (nerve damage in the hands and feet), low while blood cell counts with and without fever.

This study concluded that A+AVD was a safe and highly effective treatment in high-risk advanced cHL patients over the long-term.

This study was funded by Takeda Pharmaceutical, the manufacturers of brentuximab vedotin.