Abstract P036

Interim PET-Adapted De-escalation Chemotherapy Regimen for Advanced Stage Classical Hodgkin Lymphoma Using Brentuximab Vedotin, Pembrolizumab, Doxorubicin, and Dacarbazine: Phase 2 Study — Updated Follow-up

Background: Brentuximab vedotin(Bv), nivolumab, and pembrolizumab (P) have changed frontline therapy for advanced-stage classical Hodgkin lymphoma (AS cHL). GHSG HD18/HD21 showed PET-adapted strategies can reduce treatment without compromising efficacy. We evaluated BvP+AD with PET-adapted de-escalation to reduce chemotherapy exposure.

Methods: Pts with newly diagnosed AS or stage II bulky (≥10 cm) cHL received 3 cycles BvP+AD (Bv 1.2 mg/kg, P 400 mg Q6W, doxorubicin/dacarbazine standard dosing). P was dosed C1D1, C2D15, C4D1, and C5D15. Pts with interim PET DS1–2, or DS3 with ≥90% TMTV reduction after cycle 3, received 3 additional cycles BvP only. Pts with DS4–5 or DS3 with <90% TMTV reduction completed 6 total cycles BvP+AD. Primary endpoint was EOT CR rate; secondary endpoints included safety, ORR, and PFS.

Results: 25 pts enrolled: median age 30 (17–64), female 48% (12); stage II bulky 32% (8), stage III/IV 68% (17); non-Hispanic White 64% (16), IPS ≥3 20% (5), extranodal disease 52% (13). All pts completed interim PET: DS1 2, DS2 16, DS3 7; all DS3 pts had ≥90% TMTV reduction. All pts de-escalated to BvP only. EOT PET: DS1 5, DS2 15, DS3 2, DS4 3. EOT CR was 88% (22/25). Of 3 pts with DS4, all achieved CR by subsequent PET follow-up. At median follow-up 18.9 mo (14.2–26.4), 24/25 pts (96%) remain progression-free, with 1 progression at 13.3 mo (Figure 1). No consolidative RT was administered.

AEs: Most common any-grade AEs were PSN 80% (20), nausea 80% (20), fatigue 60% (15), ALT increased 56% (14), and alopecia 56%(14). PSN was G1 in 54%(16), G2 in 16% (4) , and no G3; PSN resolved in 40% (8/20) by last follow-up. G3 AEs included ALT elevation (3), AST elevation (1), neutropenia (2), diarrhea (1), and generalized muscle weakness (1); all resolved. No neutropenic fever occurred. IMAEs included thyroid dysfunction 16%(4), G2 pneumonitis 1, and G3 diarrhea 1. Three SAEs occurred: fever, suspected pneumonitis, and UTI/fever. Two pts discontinued P for G3 LFT abnormalities; 4 had Bv dose reduction for G2 PSN.

Conclusions: BvP+AD with PET-adapted de-escalation showed favorable safety and durable efficacy in frontline AS cHL. All pts met de-escalation criteria, reducing anthracycline/alkylator exposure by 50%, with no RT, 88% EOT CR, and 96% progression-free at 18.9 mo. Longer follow-up and larger cohorts are needed.