POST-AUTHORISATION OBSERVATIONAL SAFETY STUDY OF BRENTUXIMAB VEDOTIN IN RELAPSED/REFRACTORY HODGKIN LYMPHOMA AND SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA: ARROVEN STUDY

Introduction: Brentuximab vedotin (BV) has conditional approval in Europe for the treatment of adult patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). ARROVEN is an ongoing, multi-centre, post-authorisation safety study required by the European Medicines Agency to further evaluate BV’s safety profile in a real-world patient population. Currently available data will be presented. Methods: The objectives of ARROVEN are to evaluate the occurrence of serious adverse events (SAEs) and AEs of special interest considered related to BV; peripheral neuropathy, neutropenia, infections, hyperglycaemia, and hypersensitivity reactions. The study also aims to identify peripheral neuropathy risk factors. R/R CD30+ HL and sALCL patients aged ≥18 years are eligible if planned to start or recently commenced BV as part of routine practice. No study specific visits are mandated; safety data are collected from information recorded in medical records every ~3 months until death, withdrawal or loss of follow-up. Results: Between June 2013 and January 2015 62 patients (mean age 47.6 years [range 19–82]) were enrolled at 21 sites; 39 HL, 18 sALCL (5 unknown). Patients received a median of 4 treatment cycles (range 1–12). AEs were reported in 45 patients, the most common (n≥4) included peripheral neuropathy (n=18), infections (n=14), neutropenia (n=13), hypersensitivity reactions, and lethargy (each n=4). No hyperglycaemia events were reported. In the 18 patients with peripheral neuropathy, all 21 events were ‘sensory, motor, or other’; peripheral neuropathy risk factors are not evaluable at this time. Grade ≥3 AEs were reported in 24 patients; grade ≥3 AEs in >1 patient included infections (n=8), neutropenia (n=6), and peripheral neuropathy (n=2). Grade 4 toxicity occurred in 7 patients and included infection (n=4), progression with sepsis (n=3), neutropenia (n=2), thrombocytopenia (n=1), and tumour lysis syndrome (n=1 sALCL patient). SAEs were reported in 21 patients including 11 reported drug-related SAEs, the most common (n≥2) were infection (n=9) and peripheral neuropathy (n=4). No cases of progressive multifocal leukoencephalopathy, Stevens-Johnson syndrome, toxic epidermal necrolysis or acute pancreatitis were reported. Two patients discontinued BV, 1 due to grade 5 multi-organ failure during cycle 1 and 1 due to grade 3 pleural effusion plus grade 5 bronchopneumonia during cycle 4. Four patients died on study, 3 due to pneumonia and 1 due to disease progression. Conclusions: These data indicate that BV is associated with a manageable and tolerable safety profile in the conditionally approved indications. The severity and frequency of toxicities observed are consistent with the safety profile of BV reported in the pivotal phase ll trials. The ARROVEN trial is ongoing with a planned recruitment of 500 participants.