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That is supported by data that show escalated BEACOPP is a very effective treatment. It doesn’t improve OS, but it clearly improves disease-free control, so it makes sense for some patients with advanced-stage disease to start with a more intensive treatment and then back off.

The findings in this study will certainly have an impact on some centers in Europe. However, in the United States, outside of the pediatric population, most adults are treated with ABVD rather than escalated BEACOPP regardless of their risk factors. Thus, where ABVD is the standard of care, these data likely will not have an impact.

Brentuximab vedotin combinations yield encouraging response rates in elderly Hodgkin’s lymphoma

Brentuximab vedotin (an anti-CD30 antibody-drug conjugate) conferred 100% objective response rates when combined with dacarbazine or bendamustine for the first-line treatment of older patients with Hodgkin’s lymphoma, according to results of an interim analysis presented at the ASH Annual Meeting and Exposition. However, bendamustine (Treanda, Cephalon) appeared too toxic for the older patient population.  Peter Martin, M.D., was invited by Healio.com/HemOnc Today to give a guest perspective on the study. Read the full story here.

When we think of Hodgkin’s lymphoma, we think of it as a disease of younger people. But, there’s a bimodal distribution, and people who are older have an increased incidence of Hodgkin’s lymphoma — it takes off again after age 60 years. Still, the vast majority of studies have focused on younger patients.

In recent years, we have started to look at older patients and have realized they are not as well served with existing therapies. They may have a more aggressive form of Hodgkin’s lymphoma, and because they do not tolerate treatments as well, they have worse outcomes.

The question is, can we improve the efficacy of existing therapies while simultaneously reducing toxicity? It is not a new question, but it is a different bar when considering a 20-year-old who has a survival rate of 85% — and the focus is to reduce toxicity — vs. a 65-year-old with a differently expected outcome.

Brentuximab vedotin is clearly active based on other studies, and it can be combined with chemotherapy that is well tolerated by older people. Yasenchak and colleagues chose bendamustine based on the fact that it has well-defined activity in Hodgkin’s lymphoma, and they chose dacarbazine because it is also an alkylator and a vital part of the ABVD regimen (doxorubicin, bleomycin, vinblastine and dacarbazine). Both drugs have been combined with brentuximab vedotin in other studies.

The overall response rates were high in both arms at 100% and the complete response rate was higher in the bendamustine arm (81%) than in the dacarbazine arm (68%).

Interestingly, the investigators found that the combination with bendamustine was not as well tolerated as might have been expected. Sixty-percent of the patients in the bendamustine arm had a serious adverse event compared with 9% in the dacarbazine arm, and grade 3 to grade 4 toxicities also were significantly higher. That already is a bit of failure when you are trying to come up with a therapy that is better tolerated. In fact, they stopped the bendamustine arm because of the high rate of serious adverse events.

But what were those adverse events? That wasn’t entirely clear in the presentation at the ASH Annual Meeting. Although the bendamustine arm had a lot of toxicity, I still wonder if there is not a way to modify it and move forward with it because of the response rates. I am having a hard time writing off that combination completely.

It is still too early to say that the combination of brentuximab vedotin and chemotherapy should become the standard of care in this setting, but there is enough here to suggest that this approach is worthy of larger studies.