Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy in older patients ineligible for chemotherapy
Mené sur 22 patients âgés atteints d'un lymphome hodgkinien classique de stade avancé et inéligibles à une chimiothérapie (âge : supérieur ou égal à 60 ans ; durée médiane de suivi : 63,8 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, de la durée de la réponse, de la survie sans progression et de la survie globale, et la toxicité du brentuximab védotin en combinaison avec la dacarbazine ou le nivolumab en traitement de première ligne
Older patients with advanced-stage classical Hodgkin lymphoma (cHL) have inferior outcomes compared with younger patients, potentially due to comorbidities and frailty. This noncomparative phase 2 study enrolled patients ≥60 years with cHL unfit for conventional chemotherapy to receive frontline brentuximab vedotin (BV; 1.8 mg/kg) with dacarbazine (DTIC; 375 mg/m2) (Part B) or nivolumab (Part D; 3 mg/kg). In Parts B and D, 50% and 38% of patients, respectively, had ≥3 general comorbidities or ≥1 significant comorbidity. Of the 22 patients treated with BV-DTIC, 95% achieved objective response and 64% achieved complete response (CR). With median follow-up of 63.6 months, median duration of response (mDOR) was 46.0 months. Median progression-free survival (mPFS) was 47.2 months; median overall survival (mOS) was not reached. Of 21 patients treated with BV-nivolumab, 86% achieved objective response and 67% achieved CR. With 51.6 months of median follow-up, mDOR, mPFS, and mOS were not reached. Ten patients (45%) with BV-DTIC and 16 patients (76%) with BV‑nivolumab experienced grade ≥3 treatment-emergent adverse events; sensory peripheral neuropathy (PN) (27%) and neutropenia (9%) were most common with BV-DTIC and lipase increased (24%), motor PN (19%), and sensory PN (19%) were most common with BV‑nivolumab. Despite high median age, inclusion of patients up to 88 years, and frailty, these results demonstrate safety and promising durable efficacy of BV-DTIC and BV-nivolumab combinations as frontline treatment, suggesting potential alternatives for older patients with cHL unfit for initial conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806.