How does brentuximab vedotin perform long-term for advanced Hodgkin lymphoma?

This study presents 5-year results for the targeted antibody therapy brentuximab vedotin (BV; Adcetris) for patients with advanced Hodgkin lymphoma (HL) who had not been previously treated. It found that BV with chemotherapy led to less recurrence of HL compared to chemotherapy alone.

The outcomes for patients with the blood cancer HL have improved dramatically over the past several decades. This includes patients with advanced HL, which has spread to both the upper and lower part of the body. Most patients with advanced HL can achieve long-term remission with the chemotherapy regimen ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). However, roughly 30% will not be completely treated by ABVD. Also, ABVD can cause side effects including infertility or a second treatment-related cancer. A component of the regimen, bleomycin, can cause lung damage. More aggressive chemotherapy regimens can lead to less recurrence of HL, but they also have worsened side effects.

Brentuximab vedotin (BV) is a targeted antibody therapy that is effective against HL. The antibody portion of BV attaches to a specific molecule, CD30, which is on HL cells. BV delivers a dose of the chemotherapy drug vedotin directly to the lymphoma cells. BV is effective against HL which has relapsed (returned) after a previous treatment with chemotherapy. BV can also be used together with chemotherapy for newly diagnosed advanced HL. This regimen is known as A+AVD (BV, doxorubicin, vinblastine, dacarbazine). After two years, fewer patients treated with A+AVD have their advanced HL progress (worsen) compared to ABVD. However, it is not clear what are the long-term outcomes of this treatment.

This study included 1334 patients with advanced HL who had not been previously treated. Half of the patients were randomly assigned to treatment with A+AVD. The other patients were treated with the chemotherapy regimen ABVD. Patients were followed for an average of 60.9 months.

Significantly more patients treated with A+AVD had at least five years before the cancer progressed (82.2% vs. 75.3%). A+AVD was associated with a 32% lower risk of disease progression compared to ABVD.

It has become more common to guide treatment using positron emission microscopy (PET) scans, which can visualize cancer cells in the body. The patients in this study had PET scans performed after their first two cycles of treatment. Of those with signs of cancer after a second-cycle PET scan (PET2-positive), more patients treated with A+AVD had at least five years before progression (60.6% vs. 45.9%).

Nerve damage in the body was a side effect of both treatments, but it was more common in the A+AVD group (67% vs. 43%). Nerve-related symptoms improved over time for most patients. After five years, 19% of A+AVD patients and 9% of ABVD patients continued to have symptoms such as tingling, numbness, or weakness.

A second type of cancer developed for 3% of patients in the A+AVD group and 4% in the ABVD group.

44 female patients in the A+AVD group became pregnant, while 21 female patients in the ABVD group became pregnant. There was a higher proportion of these pregnancies continuing past the first trimester in the A+AVD group (87% vs. 75%). Although 58% of patients were under age 40 years, it is not clear how many patients tried to become pregnant.

This study found that brentuximab vedotin plus chemotherapy for the initial treatment of advanced HL leads to less long-term progression than ABVD chemotherapy.

For patients whose HL relapses (returns), BV is one of the most common secondary treatments. Patients who use A+AVD as an initial treatment will have to use alternate secondary treatments if their cancer relapses. This study received funding from Seagen, the manufacturer of BV.