Brentuximab Vedotin Combination: Potential New Front-Line Option for Hodgkin Lymphoma

The 59th Annual Meeting of the American Society of Hematology (ASH) was held from 9 to 12 December 2017 in Atlanta, Georgia. Upwards of 25,000 hematologists, scientists, and healthcare professionals gathered to discuss the cutting edge of hematology and hematologic malignancies, ranging from basic research to late-stage clinical trials. Throughout the rest of the month, we will be highlighting some of the abstracts presented at the ASH Annual Meeting with the biggest potential to influence clinical practice.

At the plenary session, Joseph Connors, MD (British Columbia Cancer Agency, Vancouver, British Columbia, Canada), presented eagerly awaited results from the randomized, multicenter ECHELON-1 trial (N = 1334), which examined brentuximab vedotin (BV) plus doxorubicin, vinblastine, and dacarbazine (AVD) in comparison to standard ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in previously untreated patients with stage III/IV Hodgkin lymphoma.

The ABVD regimen is among the most commonly used front-line treatments for patients with advanced Hodgkin lymphoma. The goal of front-line chemotherapy is to cure patients without the need for additional therapy. However, up to 30% of patients relapse after front-line ABVD treatment.  Brentuximab vedotin, a CD30-targeting antibody-drug conjugate (ADC), is currently the standard of care for patients with relapsed/refractory Hodgkin lymphoma and demonstrated favorable efficacy and an acceptable toxicity profile in a phase I front-line dose escalation trial in combination with AVD. This was the basis for the evaluation of this regimen in the phase III ECHELON-1 trial.

The primary endpoint in this study was modified progression-free survival (PFS), which defined a progression event as progression, death, or evidence of noncomplete response (based on independently assessed positron-emission tomography [PET] results) followed by subsequent anticancer therapy. At a median 24.9 months follow-up, the BV containing combination was associated with a superior modified PFS compared to that found with standard ABVD (HR 0.77, P = .035). The estimated 2-year modified PFS was 82.1% in patients receiving BV plus AVD and 77.2% in patients receiving ABVD. This corresponded to a 23% reduction in the risk of progression, death, or need for additional anticancer therapy. Overall, 33% fewer patients treated with BV plus AVD received subsequent chemotherapy or high-dose chemotherapy and transplant compared with the patients treated with ABVD.

Brentuximab vedotin plus AVD was associated with increased grade 3 neutropenia (58% vs 45%) and febrile neutropenia (19% vs 8%) compared to ABVD. However, when patients on the experimental arm received primary prophylaxis with granulocyte colony stimulating factor (G-CSF), rates of neutropenia ≥ grade 3 were greatly reduced (29% with prophylaxis compared to 70% without). Prophylactic G-CSF had a similar impact on rates of febrile neutropenia and treatment-related infection and is now recommended for all patients receiving the BV plus AVD regimen. The experimental arm was also associated with an increase in all grade peripheral neuropathy compared to ABVD (67% vs 43%), though this was reversible in 67% of patients. Importantly, rates of interstitial lung disease were much lower in patients receiving BV plus AVD compared to ABVD (2% vs 7%), indicating that exclusion of bleomycin from first-line treatment is an effective strategy for managing this serious and sometimes fatal adverse event.

Dr Connor concluded that these results support the superiority of BV plus AVD compared to standard ABVD, based both on improved modified PFS and the manageable toxicity profile.

Results from this study were simultaneously published in the New England Journal of Medicine.

 
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