Dr Alison Moskowitz Discusses When to Use Brentuximab Vedotin in Hodgkin Lymphoma

Because brentuximab vedotin is so effective in the relapsed and refractory setting, there has been a lot of excitement around assessing the treatment earlier in Hodgkin lymphoma, explained Alison J. Moskowitz, MD, medical oncologist, clinical director, lymphoma inpatient unit, Memorial Sloan Kettering Cancer Center.

How has brentuximab vedotin changed the treatment strategy for patients with Hodgkin lymphoma and how has it impacted clinical outcomes?

Brentuximab vedotin was originally evaluated in the relapsed and refractory setting for Hodgkin lymphoma, and that’s where it was initially approved. I would say in that setting, it absolutely prolongs patient survival, and that’s because before brentuximab was around, we didn’t have very many options for patients who had relapsed, for example, after an autologous stem cell transplant. So, the median survival at the time, before brentuximab was around, was 2 years, and now, that brentuximab is around, it’s significantly longer for those patients.

But of course it’s because brentuximab is highly active and fairly well-tolerated that there’s been a lot of excitement to try to see if it can impact the treatment for Hodgkin lymphoma earlier on in the treatment, and the biggest data with regard to brentuximab was the recent ECHELON-1 study where it was evaluated in the front-line setting. On that study, patients were randomized to either 6 cycles of ABVD [doxorubicin, bleomycin, vinblastine and darcarbacine] chemotherapy or 6 cycles of brentuximab plus AVD chemotherapy. The bleomycin was not included in that regimen because it was found that there is an interaction between brentuximab and bleomycin where there’s a significantly high rate of pulmonary toxicities when you keep those drugs together.

So, between those 2 arms, the study ended up being a positive study where there was an improvement in progression-free survival (PFS). The primary end point of the study was actually modified PFS, which is lightly a little different. But, basically, there was an improvement for patients who received brentuximab plus AVD. The concern, or the criticism, of the study was that the difference in the 2 arms was not as high as we would have liked. There was only about a 5% difference between the 2 arms, and the addition of brentuximab to the treatment does add some costs, such as toxicity. There are higher rates of neutropenic fever, requiring that every patient get growth factor when they get brentuximab plus AVD. There’s higher rates of neuropathy, and then of course brentuximab happens to be quite expensive, so then there’s added costs in that way.

So, when looking at the data with regard to the ECHELON-1 study, there are certain groups that seem to benefit more with the addition of brentuximab and those were patients who had stage 4 disease, those were male patients, those were patients with greater than 1 extra nodal site of disease. So, those are patients who we consider to be higher risk, those are patients I could consider using brentuximab for, particularly patients who have an international prognostic score of 4 or more.

But otherwise, for the majority of the patients, I am not using brentuximab plus AVD treatment because I think we see very good results with the Rathl approach, and it’s much better tolerated.