ISHL13 Abstract T088

Updated Results from the Phase 2 KEYNOTE-667 Study: Pembrolizumab (pembro) in Children and Young Adults With Low-Risk Classical Hodgkin Lymphoma (cHL) and Slow Early Response (SER) to Front-Line Chemotherapy (chemo)

Background: KEYNOTE-667 (NCT03407144) evaluated pembro + chemo consolidation +/- involved-site radiotherapy (ISRT) followed by pembro maintenance in pts with cHL and SER to front-line chemo. Prior results for pts with low-risk cHL and SER to front-line ABVD induction showed consolidation with pembro + AVD + ISRT followed by maintenance pembro had manageable safety and resulted in 56% of pts having PET-negative disease by BICR; 67% of pts had PET-negative disease by investigator review and received a reduced dose of ISRT. We present additional follow-up of pts with low-risk cHL and SER to ABVD.

Methods: Pts aged 3-25 y with newly diagnosed stage IA, IB, or IIA cHL received 2 cycles of ABVD followed by early response assessment (PET and CT/MRI). Pts with rapid early response received nonstudy therapy. Pts with SER (ie, Deauville score [DS] 4 or 5) received consolidation with pembro 2 mg/kg up to 200 mg (3-17 y) or 200 mg (18-25 y) IV Q3W + 2 cycles of AVD followed by late response assessment (LRA; PET, MRI/CT). All pts with SER received ISRT (21.6 Gy for complete PET response [ie, DS 1-3]; 30.6-36 Gy for partial PET response [ie, DS 4 or 5]) followed by maintenance pembro for ≤17 cycles. Primary end point: ORR by BICR per Cheson 2007 IWG criteria. Secondary end points included PET negativity after AVD and safety.

Results: 78 pts with low-risk cHL enrolled; 10 had SER to ABVD and received pembro + AVD. Median follow-up at data cutoff (Feb 29, 2024) was 19.9 mo (range, 5.6-44.8). Of 10 pts with SER, 4 completed consolidation and maintenance, 1 was ongoing, and 5 discontinued due to CR. Pts received a median of 11.5 doses of pembro (range, 5-17); median time on pembro was 7.4 mo (range, 3.5-11.3). All 10 pts who received pembro + AVD had an LRA, of whom 6 (60%) were PET negative by BICR (7 [70%] PET negative by investigator review). ORR was 100% (95% CI, 69-100; 9 CR; 1 PR). TRAEs during consolidation occurred in 8 pts (80%; grade 3 or 4 in 4 pts [40%]). No pts discontinued or died due to TRAEs. 7 pts (67%) had an AE related to pembro (grade 3 in 3 pts [30%]). 3 pts (30%) had an immune-mediated AE (all grade 1 or 2 hypothyroidism).

Conclusion: With 20 mo of follow-up, pembro + AVD consolidation followed by pembro maintenance continued to have manageable safety in pts with low-risk cHL and SER to ABVD. 60% of pts had a PET-negative response at LRA by BICR; 70% of pts had a PET-negative response by investigator review and received a reduced dose of ISRT.