Pembrolizumab in Pediatric and Young Adults Patients With Newly Diagnosed Classical Hodgkin Lymphoma and Slow Early Responders to Frontline Chemotherapy: The Phase 2 KEYNOTE-667 Study
Slow-early response (SER) to initial chemotherapy (chemo) and added radiotherapy (RT) exposure increases the risk for relapse and toxicity in patients (pts) with classical Hodgkin lymphoma (cHL). Pediatric and young adult pts with cHL and SER received pembrolizumab (pembro) + chemo in the open-label, phase 2 KEYNOTE-667 study (NCT03407144). We present interim data in pts with high-risk cHL (group 2) and SER to frontline chemo.
Eligible pts in group 2 were aged 3-25 y with newly diagnosed stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL. After 2 cycles of vincristine, etoposide, prednisone/prednisolone, doxorubicin (OEPA), pts with SER (Deauville score 4 or 5) received ≤17 doses of pembro 2 mg/kg to 200 mg (3-17 y) or 200 mg (18-25 y) IV Q3W + 4 cycles of cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28). After COPDAC-28 consolidation, pts with SER and were PET-positive (Deauville score 4 or 5) received RT + ≤17 doses of pembro; pts with SER and were PET-negative (Deauville score 1-3) received only pembro for ≤17 doses. Safety analyses included pts with SER who received ≥1 dose of pembro; efficacy analyses included pts who completed post-COPDAC-28 response assessment. The primary end point was ORR by blinded independent central review (BICR) per IWG 2007 criteria in pts with SER. Secondary end points included post-COPDAC-28 PET-negative rate, RT exposure details, and safety. Data cutoff was Nov 22, 2021.
Group 2 included 30 pts with high-risk cHL; median age was 15 y (range, 6-19), 13 (43%) pts had bulky disease, and 19 (63%) had Ann Arbor stage IV disease. At data cutoff, 23 (77%) pts had adverse events (AEs) and 6 (20%) had AEs grade ≥3; 14 (47%) pts had treatment-related AEs (TRAE) and 2 (7%) had TRAEs grade ≥3. Serious AEs occurred in 3 (10%) pts (1 [3%] pt had grade 2 immune-mediated hypothyroidism). After 9.6 mo (range, 2.5-21.2) of median follow-up, 6 (20%) pts completed and 24 (80%) were continuing treatment; median time on treatment was 3.3 mo (range, 0-11.8). Of the 25 (83%) pts who had a post-COPDAC-28 assessment, 17 (68%) were PET-negative by BICR; 18 (72%) pts by investigator assessment.
Pembro + COPDAC-28 in pediatric and young adult pts with high-risk cHL and SER to frontline chemo demonstrated acceptable safety. Thus, 68% of pts with PET-negative response were spared RT after consolidation. Early data show that pembro may enhance responses to chemo in this pt population.