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

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are 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 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 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% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. 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.

Evidence-Based Minireview: What is the optimal timing of anti-PD-1 antibodies in relapsed classical Hodgkin lymphoma?

A 26-year-old woman was initially diagnosed with stage III classical Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for 6 cycles and relapsed 9 months after completing therapy. She was treated with salvage chemotherapy followed by an autologous transplantation and 1 year of brentuximab vedotin (BV) maintenance therapy. She now presents 1 year later with relapsed disease above and below the diaphragm. What treatment would you recommend for this patient?

PD-1 blockade in Hodgkin's lymphoma: learning new tricks from an old teacher.

INTRODUCTION: Classical Hodgkin's Lymphoma (cHL) is characterized by genetic reliance on the PD-1 pathway. Rapid accumulation of data describing the role and efficacy of PD-1 and its blockade warrants a focused review. AREAS COVERED: In this article, we will review the unique biologic features that predispose cHL to PD-1 inhibition, current data regarding the safety and efficacy of PD-1 inhibitors in the treatment of cHL, biomarkers of immune response, ongoing clinical trials with PD-1 inhibitors, as well as areas of uncertainty. Expert commentary: The biologic and genetic underpinnings of cHL make it unique among all malignancies in its exquisite sensitivity to PD-1 inhibition. High response rates to single agent PD-1 inhibitors in early phase clinical trials serve as further proof of concept. These data strongly support continued clinical investigation of the evolving role of PD-1 inhibition in classical Hodgkin's lymphoma, including the optimal sequence, setting, and combination to best exploit the immunologic properties of this disease.