Randomized Phase II Study of Brentuximab-Vedotin With High-Dose Chemotherapy in CD30 Positive Lymphoma.

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.