P020 | EXTENDED LEAD-IN PHASE OF BRENTUXIMAB VEDOTIN AND SHORTENED AVD IN OLDER PATIENTS (>60 YEARS) WITH ADVANCED HODGKIN LYMPHOMA (HL) AND HIGH COMORBIDITY BURDEN (ECOG≥2 AND/OR CIRS-G>10).

Introduction: Older patients (pts) with Hodgkin Lymphoma (HL) have worse outcomes due to biological characteristics, poor performance status (PS), and comorbidities. Standard treatment may not suit many pts due to reduced tolerance, including high Doxorubicin load. We investigated whether Brentuximab Vedotin (BV) lead-in could manage symptomatic disease, minimize therapy-related events, and shorten chemotherapy without affecting outcomes. Methods: Naïve pts (>60 years) with advanced HL, ECOG PS≥2 and/or CIRS-G>10, received 6 cycles of BV followed by 4 cycles of AVD (Doxorubicin, Vinblastine, Dacarbazine). Pts underwent G-CSF prophylaxis. Response was assessed by Lugano 2014 criteria after BV lead-in and every two AVD cycles. Serial cytokine evaluations (TARC, IL-10, IL-6, SIRPγ, TGF-β1, CD47) were performed, and toxicity was monitored by CTCAE v5.0. Data were analyzed via the IRB-approved LYMRO-22 study. Results: Nine pts (4 males) with median age 67 years (r 62-75) and stage III-IV (n=7) or IIBE/X (n=2) were treated (May 2021-May 2024). ECOG PS was ≥2 in 67%; median CIRS-G was 11 (r 7-19) and 67% had B symptoms. Six pts completed 6 BV, two discontinued after 5 and one received 4 courses. All pts received 4 AVD, except one discontinuing after 3 cycles due to G3 vomiting/dysionemia. During BV lead-in no G≥2 peripheral neuropathy (PN) occurred. G≥3 neutropenia (22%), G≥3 anemia (11%) and G1 PN (44%) were reported. AVD relative dose intensity was maintained in 89% of pts. Overall response rate was 100%, with complete remission (CR) of 55% at the end of BV lead-in. After AVD all pts achieved CR and 3 were consolidated with radiotherapy. At a median follow-up of 25.4 months (r 7.3-55.1), the 2-year progression-free and overall survival were 83.3% (SE ±15.2) and 100%, respectively. Median CR duration was 14.6 months (r 1.5-45.8). Plasma TARC levels decreased significantly (r −28.9% to −91.3%; p=.0039) at end-of-treatment (EoT), while other cytokine patterns showed variable changes. In contrast, plasma CD47 levels increased up to 970-fold at EoT versus baseline (Figure 1). Conclusions: Although BV monotherapy shows limited effectiveness, extended BV lead-in may allow older patients with significant comorbidities to safely complete 4 AVD, achieving durable CRs with reduced Doxorubicin exposure. Biomarker analyses confirmed TARC as a reliable response marker and revealed an unexpected increase in soluble CD47 associated with response, warranting further investigation.