Pembrolizumab Combo Shows Efficacy in Pediatric High-Risk Hodgkin Lymphoma

Pembrolizumab (Keytruda) plus cyclophosphamide, vincristine, prednisone, and dacarbazine for 28-day cycles (COPDAC-28) with or without radiotherapy demonstrated promising antitumor activity among patients 3 to 25 years old with newly diagnosed classic Hodgkin lymphoma (cHL) who had slow and early responses to chemotherapy, according to updated findings from the phase 2 KEYNOTE-667 trial (NCT03407144) presented in a poster at the European Hematology Association (EHA) 2026 Congress.

Among all evaluable patients treated on the trial (n = 84), the objective response rate (ORR) was 98% (95% CI, 92%-100%), with 75% of patients attaining a complete response (CR). Moreover, the late response assessment by blinded independent central review (BICR) showed a rate of 98%, with a PET negativity rate of 71%. Per investigator assessment, the late response rate was 98%, with a PET negativity rate of 71%.

A Kaplan-Meier estimate of event-free survival (EFS) per Cheson 2007 International Working Group (IWG) criteria by BICR showed 17 events by the 43.4-month (range, 24.7-67.5) cutoff point, with a median value that was not reached (NR; 95% CI, NR-NR). The 24- and 36-month EFS rates were 85% and 81%, respectively. Moreover, at the time of data cutoff, no fatalities were reported, for a 36-month overall survival (OS) rate of 100%.

“After a median follow-up of 43.4 months, pembrolizumab plus COPDAC-28 consolidation with or without radiotherapy followed by pembrolizumab maintenance continued to show promising antitumor activity,” Christine Mauz-Körholz, MD, PhD, professor in the Department of Pediatric Hematology and Oncology and an attending physicians at Martin Luther University Halle-Wittenberg in Halle, Germany, wrote in the presentation with study coinvestigators. “Safety was manageable and consistent with prior analyses; no news safety signals were identified. The results of this analysis continue to support further investigation of pembrolizumab plus COPDAC-28 as consolidation therapy in children and young adults with high-risk cHL and [slow early response] to front-line [vincristine, etoposide, prednisone, and doxorubicin (OEPA)].”

Patients with stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB newly diagnosed cHL who were 3 to 25 years old were eligible for enrollment on the trial. Additional inclusion criteria included measurable disease, a Lansky Play-Performance scale score of at least 50 for patients up to 16 years old, and a Karnofsky Performance Status Scale score of at least 50 for those 17 years and older.

Those with newly diagnosed cHL underwent OEPA induction for 2 cycles. Those who were PET positive per early response assessment received COPDAC-28 for 4 cycles plus pembrolizumab at 2 mg/kg up to a maximum of 200 mg intravenously every 3 weeks. Following another late response assessment, patients with a positive PET scan received radiotherapy as maintenance, with all patients continuing pembrolizumab every 3 weeks for up to 17 cycles.

On the study, 93% of patients were 3 to 17 years old, 54% were male, and 73% were White. Most patients had bulky disease (52%), nodular sclerosis (81%), Ann Arbor stage IV disease (63%), and Lymphoma B symptoms (63%).

The primary end point of the study was ORR per Cheson IWG criteria by BICR. Secondary end points included PET negativity—represented by a Deauville score of 1 to 3—after consolidation, 2-year EFS, OS, and safety.

Any-grade treatment-emergent adverse effects (TEAEs) were observed among 95% of patients, with grade 3 or 4 TEAEs observed in 36%. Serious TEAEs or those leading to treatment discontinuation occurred in 24% and 5% of patients, respectively; none died due to TEAEs. Treatment-related AEs (TRAEs) occurred at a rate of 76%, with 19% of patients experiencing grade 3 or 4 events. Serious TRAEs or those leading to discontinuation were observed in 8% and 5% of patients, none of which led to death.

The rate of any immune-mediated AE or infusion reaction was 14%, of which 2% were grade 3 or 4. Similarly, 2% of patients had immune-mediated AEs or infusion reactions deemed serious or which led to treatment discontinuation, and no deaths were observed.

Reference

Mauz-Körholz C, Vinti L, Daw S, et al. Pembrolizumab in children and young adults with high-risk classic Hodgkin lymphoma with slow early response to front-line chemotherapy: updated results from KEYNOTE-667. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PS2015.