Brentuximab Vedotin Leads Treatment Progress in Hodgkin Lymphoma

Syed Rizvi, MD

Longer follow-up of the ECHELON-1 trial solidified a benefit in progression-free survival (PFS) with the combination of brentuximab vedotin (Adcetris) and doxorubicin, vincristine, and dacarbazine (AVD) compared with AVD plus bleomycin (ABVD) in patients with Hodgkin lymphoma, explained Syed Rizvi, MD.

In the multicenter, open-label study, patients treated with brentuximab vedotin plus AVD (A+AVD) had a 31% reduction in the risk of disease progression or death versus ABVD, which was statistically significant, after a median follow-up of 48.4 months (HR, 0.69; 95% CI, 0.542-0.881).^1,2 At 4 years, the PFS rate was 81.7% with the brentuximab vedotin regimen versus 75.1% with ABVD.

In March 2018, the FDA approved brentuximab vedotin for use in combination with chemotherapy as a frontline treatment for adult patients with stage III/IV classical Hodgkin lymphoma, based on earlier findings from the ECHELON-1 trial.

“The skepticism that we had is not as [prevalent] as it used to be. We are increasingly becoming open-minded to the idea [of A+AVD],” said Rizvi, an assistant professor in the Department of Internal Medicine at UT Southwestern Medical Center.

Now, investigators are evaluating brentuximab vedotin in combination with immunotherapy (NCT01716806), Rizvi said. Other treatments, such as CAR T-cell therapy and BTK inhibitors, are also being explored in this patient population, Rizvi added.

In an interview during the 2020 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Rizvi discussed recent therapeutic advances in advanced-stage Hodgkin lymphoma.

OncLive: What is the current standard-of-care treatment for patients with Hodgkin lymphoma?

Rizvi: ABVD has been the standard of care [in advanced Hodgkin lymphoma] for almost 14 years. However, about 30% of patients do not respond to [treatment], and the PFS rate is not 100%. We are trying to identify who the nonresponders are early on so we can get them appropriate treatment. We also want to potentially identify therapies that can lead to better PFS and, hopefully, overall survival.

What practice-changing updates in Hodgkin lymphoma were presented at the 2019 ASH Annual Meeting?

There were [results from] the ECHELON-1 study; a lot of us were skeptical early on about the PFS data with just 2 years of follow-up. They presented data from 4 years of follow-up, and [A+AVD] still looks promising compared with ABVD. There were certainly better PFS rates reported for PET2-positive patients, so that is encouraging, too.

Certainly, [the regimen] has some complications, which are more commonly [in the form of] neutropenia and febrile neutropenia. The effects of neutropenia and peripheral neuropathy results were reported at the 4-year follow-up. Lung toxicity is certainly less with this regimen as well.

Could other combination strategies with brentuximab vedotin have potential?

Brentuximab vedotin has been out for 7 to 8 years now and was initially approved in the second-line setting. Since 2018 it has been used for upfront Hodgkin lymphoma treatment.

Brentuximab vedotin is being used in conjunction with checkpoint inhibition. That is an exciting study, and many of us are waiting for the results. We want to see how some of these high-risk patients would benefit [from this combination treatment] or [how they would] not.

For a patient with stage III/IV Hodgkin lymphoma, what factors do you take into consideration when determining their optimal treatment?

The age of the patient, their smoking history, the integrity of their lung tissue, whether they have a history of lung disease, and whether they have a history of neuropathy or a condition that predisposes them to neuropathy—those would be some of the [important factors].

ABVD was the standard [chemotherapy option] in North America, but over the past 2 years, with brentuximab vedotin being approved for up-front use, many of us are considering whether patients have [disorders, such as] lung involvement, up front. Otherwise, [patients who are] nonsmokers or have no history of cytopenia [are usually treated with] brentuximab vedotin plus AVD, and then [we omit] bleomycin altogether.

What other novel agents are moving through the pipeline in Hodgkin lymphoma?

Personally, I find checkpoint inhibitors in conjunction with brentuximab vedotin quite interesting. Some data [show that] BTK inhibitors [have] some activity in Hodgkin lymphoma, as well, [and investigators are also looking at] them in combination with some of these agents, such as checkpoint inhibitors.

Is there any rationale to explore CAR T-cell therapy in Hodgkin lymphoma?

That is being explored. CAR T-cell therapy is [an approach in which] a lot of our patients would benefit. We have had a few patients treated with CAR T-cell therapy in Houston, Texas and North Carolina who have done well posttreatment. That is certainly something that is in the pipeline and we are excited about that.

References

1. Bartlett NL, Straus DJ, Dlugosz-Danecka M, et al. Brentuximab vedotin with chemotherapy for stage 3/4 classical Hodgkin lymphoma (cHL): 4-year update of the Echeleon-1 study. Blood. 2019;134(suppl 1):4026. doi: 10.1182/blood-2019-124116.
2. Seattle Genetics and Takeda announce additional analyses of Adcetris (brentuximab vedotin) ECHELON-1 and ECHELON-2 phase 3 clinical trials at the 2019 ASH Annual Meeting [news release]: Bothell, WA, and Cambridge, MA, and Osaka, Japan. Seattle Genetics, Inc; December 9, 2019. bit.ly/2tXAswp. Accessed January 27, 2020.