# Randomized Phase II Study of Brentuximab‐Vedotin With High‐Dose Chemotherapy in CD30 Positive Lymphoma

## TL;DR

This study tested adding brentuximab-vedotin to high-dose chemotherapy in CD30-positive lymphoma patients but found no improvement in outcomes and increased lung toxicity.

## Contribution

The study provides evidence against the benefit of adding brentuximab-vedotin to BeEAM chemotherapy in relapsed CD30-positive lymphoma.

## Key findings

- Adding brentuximab-vedotin to BeEAM did not improve disease-free or overall survival.
- Two patients in the brentuximab-vedotin arm developed grade 3 pneumonitis.
- Prior exposure to brentuximab-vedotin may have reduced the potential benefit of the combination.

## Abstract

Patients with Hodgkin lymphoma (HL) or peripheral T‐cell lymphoma (PTCL) who relapse after high‐dose chemotherapy (HDCT) have a dismal prognosis. Brentuximab‐vedotin (BV) is a CD30‐targeting antibody‐drug‐conjugate (ADC) used in first‐line‐, salvage‐, and maintenance‐therapy of HL, as well as first‐line‐ and salvage‐therapy of PTCL. In phase I of this trial, we could show that BV can safely be added to BeEAM‐HDCT (bendamustine, etoposide, cytarabine and melphalan). Here, we report the randomized phase II part of the trial comparing BV‐BeEAM to BeEAM alone (ClinicalTrials.gov: NCT03187210). Primary endpoint was 1‐year disease‐free survival. Inclusion of 42 patients was planned but the study was terminated early, after a futility analysis showed lack of benefit. Twenty‐five patients (HL: 11, PTCL: 14) who were planned to undergo HDCT were included. Median age was 60 years. Patients had a median of two prior therapies, and 11 were previously exposed to BV. Patients in the standard‐arm had higher disease stage and (PTCL only) higher IPI. Duration of hospitalization, recovery of neutrophils/platelets, and infections were not significantly different between arms. No treatment related death occurred. However, two patients in the BV‐arm developed grade 3 pneumonitis. After 22 months median follow‐up, overall response‐rate, complete remission‐rate, disease‐free survival and overall survival did not differ between groups. Pre‐planned subgroup‐analyses (HL‐only, PTCL‐only, only those achieving CR) did not show benefit in any subgroup. In conclusion, adding BV to BeEAM does not improve outcomes after HDCT, and may increase pulmonary toxicity. Frequent prior exposure to BV may have limited the potential benefit of the combination.