Background: cHL occurs in a bimodal age distribution with 20-30% of diagnoses occurring in Pts aged ≥ 60 years. Outcomes have improved in the recent era. However, treatment related toxicities are common, especially for unfit and frail pts. We designed a multicenter prospective study utilizing fitness-based assessments to assign targeted cHL therapy.
Methods: Subjects had untreated cHL with an age ≥ 60 years and ECOG performance status (PS) of 0-1 or PS of 2 if decline was cHL-related. Those with Grade ≥ 2 neuropathy, known additional malignancy, and active inflammatory disease were excluded. All subjects were treated with brentuximab vedotin (BV) and pembrilizumab (Pem) for 6 weeks (Figure). Thereafter, fitness assessment, comprising activities of daily living (ADLs), instrumental ADLs, and Cumulative Illness Rating Scale-Geriatric scores were repeated. Subjects were grouped into Fit, Unfit and Frail adapted from Merli et al JCO 2021. All patients continued Pem, with additional treatment based on fitness: Fit (full dose AVD x4 cycles), Unfit (half-dose "mini" AVD x4 cycles), and Frail (BV x18 weeks). Primary objectives were to assess safety and efficacy. Target sample size was 44 participants. The study was registered on clinicaltrials.gov (NCT05404945) and supported by a research grant from Merck Sharp &Dohme LLC.
Results: Enrollment occurred from 7/2022 to 12/2025 at 3 US institutions. Due to slow enrollment and a new standard therapy for fit older cHL Pts (S1826 study: Rutherford et al JCO 2025), the study closed early. Ten pts consented to the trial and 8, with a median age of 81 years (range 66-85), were treated. After BV/Pem lead-in, 3 were allocated to the frail arm, 4 were allocated to the unfit arm, and 1 was allocated to the fit arm. 75% (n=6) completed induction. All subjects responded; best response was CR in 75% (n=6) and PR in 25%(n=2). Five related SAE’s occurred in 37.5% (n=3) of subjects. No new toxicities were identified or Grade 5 events. One subject remains on treatment.
Conclusions: Treatment with Bv/Pem-based therapy for newly-diagnosed older cHL Pts based on fitness assessments was feasible. This study also introduced a new “mini-AVD” regimen for unfit cHL Pts. Responses rates were robust in this small cohort; however, the study was closed prematurely. Further study is warranted for older cHL pts with therapy tailored according to fitness.
Craig Portell, Bethany Horton, David Brighton, Jakub Svoboda, Victor Orellana-Noia, Andrew M. Evens