Effectiveness and Safety for Re-Treatment with Brentuximab-Vedotin in Patients with Relapsed/Refractory (R/R) CD30+ Malignancies: A Retrospective Medical Chart Review Study in Spain. the Believe Study. NCT:04998331

INTRODUCTION

Brentuximab vedotin (BV) is a CD30-directed antibody-drug conjugate that is indicated in patients with R/R classical Hodgkin lymphoma (cHL), systemic anaplastic large cell lymphoma (sALCL), and CD30+ cutaneous T cell lymphoma (CTCL: mycosis fungoides [MF] and primary cutaneous anaplastic large cell lymphoma [pcALCL]). Limited data on R/R patients receiving BV retreatment showed promising clinical outcomes. The aim of this study was to describe the effectiveness and safety of BV retreatment in R/R patients with CD30+ malignancies in a real-world setting in Spain.

METHODS

A noninterventional, retrospective, multicenter, medical chart review study was conducted in 30 Spanish sites (data collection: 2014-2022). Adult patients with confirmed diagnosis of cHL, sALCL, or CTCL (MF/pcALCL) with CD30+ disease, previously treated with BV (with evidence of objective response, (OR) and having received ≥2 doses of BV as retreatment were included. Patients were followed up to ≥6 months or treatment discontinuation due to death or toxicity. This study was conducted in accordance with the Declaration of Helsinki. The primary objectives were to assess safety and antitumor activity of BV retreatment.

RESULTS

Fifty-one patients were included in the study, 43 were evaluable. At the time of initiation of BV retreatment > 50% of patients had advanced disease. The median age was 46 years (18-76), 58% males, and 90% had ECOG PS of grade 0–1. The median duration from diagnosis to end of follow-up was 6 (2–20) years. Most patients (84%) received treatments between the first course of BV and BV retreatment, median of 1 (1-5). The median time from first BV treatment to retreatment initiation was 18 (7–108) months. Thirty-three (77%) patients achieved OR; 26 (61%) CR, 7 (16%) PR and progression was observed in 6 (14%). Overall, the median time to achieve CR was 4 (0.6-24.3) months. The median number of cycles during the first course of BV was similar to the ones at retreatment: 4.5 (2-18) in cHL, 7 (3-14) in CTCL, and 6 (2-20) in sALCL. After starting retreatment with BV, a total of 9 patients (20.9%) underwent one allogenic transplant (4 [25%] with cHL, 2 [14.3%] with CTCL, and 3 patients [23.1%] with sALCL. The median PFS: 9.6 months (0.5-77.5). In total, 18 patients (45%) experienced adverse events (AEs) related to BV retreatment, mainly peripheral sensory neuropathy. Overall, severe AEs were in 8 patients (19%), mainly 1 (2.3%) peripheral motor neuropathies, 3 (7%) with peripheral sensory neuropathy (PN), 1 (2.3%) neutropenia and 3 (7%) others with clinical relevance. The median initial dose of BV retreatment was the same as in the first course of BV, 1.8 mg/kg, and was also constant in the three cohorts. Eight (19%) patients had an initial dose adjustment mostly due to peripheral neuropathy. During retreatment, 5 patients had a dose adjustment, 1.2 mg/kg: 1 patients in CTCL group and 4 patients in sALCL group. No Grade 5 events were reported during retreatment. The OS was reported for 16 patients (37.2%), mainly due to progression, which includes 9 cHL (56.2%), 4 CTCL (28.6%), and 3 sALCL patients (23.1%). Overall, the median KM time to death was 33.4 (0.5-50) months; this was 33.1 (0.5-50) in cHL group, 25.4 (2.3-25.4) in CTCL group, and - (4.9 - 31.6) months in sALCL group.

CONCLUSIONS

The BELIEVE study is the first real word evidence study in Spain that assesses the role of BV as retreatment. Safety results were manageable with dose modification or interruption. BV retreatment seems to be a promising and tolerable treatment alternative.