Abstract P038

Frontline nivolumab-AVD in older patients with advanced classical Hodgkin lymphoma: real-word experience from a single Italian centre

Background: Older patients with advanced classical Hodgkin lymphoma (cHL) are underrepresented in clinical trials because of comorbidities and frailty. Although the phase III S1826 study demonstrated improved efficacy and tolerability of nivolumab plus AVD (N-AVD) compared with brentuximab vedotin-AVD, real-world evidence remains limited. We report updated outcomes of elderly patients treated with frontline N-AVD at our institution.

Methods: We retrospectively evaluated consecutive patients aged >60 years with stage III-IV cHL treated with frontline N-AVD. Treatment consisted of nivolumab (240 mg, days 1 and 15) combined with AVD every 28 days for six cycles. Chemotherapy dose reductions were allowed at physician discretion. Responses were assessed by PET-CT. Overall response rate (ORR) included complete and partial response (CR, PR), was assessed at end-of-treatment (EOT). Progression-free survival (PFS) was defined from treatment start to progression or death from any cause. Adverse events were graded according to CTCAE ver.5.0.

Results: Eleven patients were included (median age of 71 years, range 65-85); eight (73%) were male. All had stage III-IV disease. Median IPS was 3 (range 2-5), with 64% high-risk disease (IPS ≥3). AVD dose attenuation was required in five patients (four at 50% and one at 75% of standard dose), while nivolumab was administered at full dose in all cases. Interim PET showed CR in six patients (54%), PR in four (36%), and progressive disease (PD) in one patient. At EOT, ORR was 72% (CR 63%, PR 9%); three patients experienced PD. After a median follow-up of 18 months (range 5-25), estimated 18- month PFS was 53%. Most progression events occurred within the first 10 months of treatment. One patient died from PD beyond 18 months. Progressions occurred in both dose-attenuated and full-dose groups. The most frequent toxicity was neutropenia, occurring in nine patients (82%), including grade ≥ 3 in seven (64%). Infections included pneumonia (n=2) and urinary tract (n=1). Immune-related adverse events occurred in two patients (hypothyroidism and interstitial pneumonitis).

Conclusions: In this real-world series of elderly patients with advanced cHL, frontline N-AVD demonstrated considerable response rates despite dose attenuation. Early progression remained common, likely reflecting the greater frailty and comorbidity burden of patients treated in routine practice compared with those enrolled in clinical trials.