Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma

Abstract

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A+AVD) demonstrated superior efficacy compared to bleomycin+AVD (ABVD) for the treatment of advanced-stage classic Hodgkin's lymphoma (cHL). However, there is minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 stage III and IV cHL patients treated with frontline A+AVD from January 2010 through April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median age was 37 years, and high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received six cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% CI: 24.8 - 29 months), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% confidence interval [CI], 85.9-95.0). The impact of CDB on PFS was not significant (p-value=0.15), nor was high CDB significantly associated with increased adverse events (AE). In real-world experience, A+AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

How I Follow Hodgkin Lymphoma in First Complete (Metabolic) Remission?

“…It is important to note that BV was discontinued in 10% of cases. However, the real-world data show a higher incidence of this AE [66]. In a study by Steiner et al involving 179 patients receiving BV + AVD, the rate of BVIN was 75%, with the grade 3 rate being 12%.…”