Targeted drug doubles progression-free survival in Hodgkin lymphoma

A phase 3 trial of brentuximab vedotin (BV), the first new drug for Hodgkin lymphoma in more than 30 years, shows that adults with hard-to-treat Hodgkin lymphoma given BV immediately after stem cell transplantation survived without the disease progressing for twice as long as those given placebo (43 months vs 24 months).

The findings, published in The Lancet (2015; doi:10.1016/S0140-6736(15)60583-9), are potentially practice changing for this young cancer population who have exhausted other treatment options and for whom prognosis is poor.

“No medication available today has had such dramatic results in patients with hard-to-treat Hodgkin lymphoma”, said lead author Craig Moskowitz, MD, a professor of Medicine at Memorial Sloan Kettering Cancer Center, New York, New York.

Hodgkin lymphoma is the most common blood cancer in young adults ages 15 to 35 years. Most patients are cured with chemotherapy or radiotherapy.

However, for patients who relapse, or do not respond to initial therapy, the treatment of choice is usually a combination of high-dose chemotherapy and autologous stem cell transplant (ASCT), a procedure that uses healthy stem cells from the patient to replace those lost to disease or chemotherapy. Although approximately 50% of patients who undergo this procedure are cured, treatment is palliative for the remaining patients.

BV is an antibody attached to a powerful chemotherapy drug that seeks out cancer cells by targeting the CD30 protein on Hodgkin lymphoma cells. BV sticks to the CD30 protein and delivers chemotherapy directly into the cancer cell to kill it. Recently, BV has been approved for relapsed or refractory Hodgkin lymphoma in 50 countries.

In the AETHERA phase 3 trial, Moskowitz and colleagues aimed to establish whether early treatment with BV after ASCT could prevent disease progression. They randomly assigned 329 patients with Hodgkin lymphoma age 18 years or older who were at high risk of relapse or progression after ASCT to 16 cycles of BV infusions once every 3 weeks or placebo.

At 2-year follow-up, the cancer had not progressed at all in 65% of patients in the BV group compared with 45% in the placebo group.

“Nearly all of these patients who are progression free at 2 years are likely to be cured since relapse 2 years after a transplant is unlikely,” explained Moskowitz.

BV was generally well tolerated. The most common side effects were peripheral neuropathy (67% BV vs 13% placebo) and neutropenia (35% vs12%).

According to Moskowitz, “The bottom line is that BV is a very effective drug in poor risk Hodgkin lymphoma and it spares patients from the harmful effects of further traditional chemotherapy by breaking down inside the cell, resulting in less toxicity.”

 This study was funded by Seattle Genetics Inc and Takeda Pharmaceuticals International Co.

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