A Phase II Study of Brentuximab Vedotin (BV) in the Treatment of Elderly Hodgkin Lymphoma (HL) Patients at First Relapse or with Primary Refractory Disease — FIL_BVHD01
Authors: Tonialini Lorenzo , Stefoni Vittorio , Re Alessandro , Lleshi Arben , Bonfichi Maurizio , Pinto Antonello , Bianchetti Nicola , Argnani Lisa , Zinzani Pier Luigi 
Published: October 2019

Abstract
Older age (≥60 years) has consistently been identified as an independent adverse prognostic factor for Hodgkin lymphoma (HL) survival in population-based studies and clinical trials in the last several decades. Elderly HL patients are significantly underrepresented in clinical trials and have a markedly inferior prognosis compared with younger patients. Brentuximab vedotin (BV) is an antibody-drug conjugate linking the microtubule-disrupting agent monomethylauristatin E to an anti-CD30 antibody. BV monotherapy yields an objective response rate (ORR) of 75% in relapsed HL, with a subset of patients having durable remissions at 5 years. In a retrospective analysis of BV activity in patients aged ≥60 years with relapsed HL, ORR was 56%. Although higher rates of adverse events (AEs) such as anemia, fatigue, and neuropathy were seen in older compared with younger patients, BV was tolerable overall, and a significant proportion of older patients had clinical benefit. Based upon this favorable experience, our phase II study evaluated the efficacy and safety of BV as a single agent in elderly patients at first relapse or with primary refractory HL. This was a single-arm, open-label, multicenter, clinical trial. The primary endpoint of this study was the ORR. Main secondary endpoints were: duration of response, complete remission rate, progression free and overall survival at 1 year and type, incidence, severity, seriousness, and relatedness of any adverse events occurring during the study period. ClinicalTrials.gov identifier NCT02227433.
Twenty patients were enrolled, 2 results in screening failure and 1 patient was treated in protocol violation (more of 1 previous therapy). Eighteen patients were considered for safety analysis, whereas 17 subjects were included in the efficacy analysis. BV (1.8 mg/kg) was administered as a single IV infusion on Day 1 of each 21-day cycle for a maximum of 16 cycles.
Three patients interrupted BV treatment before the first scheduled restaging (right after the IV cycle): 2 due to toxicity and 1 due to clinical progression of disease (PD). At first restaging, ORR was 52.9% (4 complete response [CR] and 5 partial response [PR]). Eight patients proceeded till the second restaging (VIII cycle) with and ORR of 17.7% (1 CR and 2 PR). Only 2 patients completed all the 16 scheduled cycles: they achieved finally a CR and a PR, respectively. These two patients are still in response at the latest available follow up. Seven patients had early treatment discontinuation due to toxicity, mainly due to neuropathy grade II-III (3 out of 7).
The objective of the study, i.e. at least 13 responses, was not reached and BV doesn't seem to be an effective single agent for elderly HL patients at first relapse. Nevertheless, prolonged disease control (more than 12 months) was registered in two patients, suggesting that some subjects can benefit from this salvage treatment.

Disclosures
Zinzani: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau; Astra Zeneca: Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees.