Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy for older patients ineligible for chemotherapy

• Published in: Blood 2024-02, Vol.143 (9), p.786-795
• Main Authors: Friedberg, Jonathan W., Bordoni, Rodolfo, Patel-Donnelly, Dipti, Larson, Timothy, Goldschmidt, Jerome, Boccia, Ralph, Cline, Vivian J. M., Mamidipalli, Adrija, Liu, Jingmin, Akyol, Alev, Yasenchak, Christopher A.
• Format: Article
• Language: English
• Subjects: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Brentuximab Vedotin; Dacarbazine; Frailty; Hodgkin Disease - pathology; Humans; Immunoconjugates; Nivolumab - adverse effects
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2022019536

•With a median follow-up of 63.6 months, mPFS of patients aged ≥60 years with cHL treated with upfront BV-DTIC was 47.2 months.•Noncomparatively, mPFS of patients aged ≥60 years with cHL treated with BV-nivolumab was not reached with a median follow-up of 51.6 months. [Display omitted] 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 aged ≥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 a 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 increased lipase (24%), motor PN (19%), and sensory PN (19%) were most common with BV-nivolumab. Despite high median age, inclusion of patients aged ≤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. Older patients with advanced-stage classical Hodgkin lymphoma (cHL) have worse outcomes than younger patients and are also often excluded from clinical trials. Friedberg et al report on a noncomparative phase 2 study for patients with cHL over age 60 unfit for conventional chemotherapy who received either brentuximab vedotin (BV) plus dacarbazine (DTIC) or BV plus nivolumab. Responses were excellent, with the regimens yielding complete response rates of 64% to 67%. Median progression-free sur