Is Pembrolizumab Active in Pediatric Patients With PD-L1–Positive Advanced Solid Tumors or Lymphoma?

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Interim analysis of the phase I/II KEYNOTE-051 trial, reported in The Lancet Oncology by Geoerger et al, indicated minimal activity of pembrolizumab in pediatric patients with programmed cell death ligand 1 (PD-L1)-positive advanced, relapsed, or refractory solid tumors; however, activity was observed in pediatric patients with relapsed or refractory Hodgkin lymphoma.

Study Details

The international study involved 155 patients aged 6 months to 17 years (12 from phase I, 143 from phase II) with more than 20 central nervous system and non–central nervous system tumor types who received 2 mg/kg of pembrolizumab every 3 weeks; the dose was selected for the ongoing phase II component after no dose-limiting toxicities at 2 mg/kg were observed in phase I. Among the 155 patients, 147 had PD-L1–positive tumors, 5 had PD-L1–negative melanoma, and 3 had missing PD-L1 status (2 with Hodgkin lymphoma and 1 with astrocytoma). Response was assessed by RECIST version 1.1 or International Neuroblastoma Response Criteria. The data cutoff for the interim analysis was in September 2018; the trial continues to enroll patients.


The median age of patients was 13 years. Median follow-up was 8.6 months.

Of 15 evaluable patients with relapsed or refractory Hodgkin lymphoma, 9 (60%) had objective response, including 2 patients who had a complete response. Among the 136 evaluable patients with solid tumors and other lymphomas, partial response was observed in 8 (5.9%; 2 patients each with adrenocortical carcinoma and mesothelioma, and 1 patient each with malignant ganglioglioma, epithelioid sarcoma, lymphoepithelial carcinoma, and malignant rhabdoid tumor).


  • Response was observed in 9 of 15 patients with Hodgkin lymphoma.
  • Response was observed in 6% of patients with other tumor types.

Adverse Events

Grade ≥ 3 adverse events occurred in 45% of patients, with the most common being anemia (9%) and decreased lymphocytes (6%); adverse events were considered treatment-related in 8% (decreased lymphocytes in 2% and anemia in 1%). Serious treatment-related adverse events occurred in 9%, with the most common being pyrexia (3%) and hypertension and pleural effusion (1% each). Adverse events led to treatment discontinuation in 5% (in 3% due to treatment-related events). Adverse events led to death in 4% of patients, with adverse events considered treatment-related in two patients (1%; pulmonary edema and pleural effusion with pneumonitis).

The investigators concluded, “Pembrolizumab was well tolerated and showed encouraging antitumour activity in pediatric patients with relapsed or refractory Hodgkin lymphoma, consistent with experience in adult patients. Pembrolizumab had low antitumour activity in the majority of pediatric tumour types, and responses were observed in only a few rare PD-L1–positive tumour types, suggesting that PD-L1 expression alone is not sufficient as a biomarker for the selection of pediatric patients who are likely to respond to PD-1 checkpoint inhibitors.

Final results of KEYNOTE-051, expected by September 2022, with the possibility for extension, will report further on the activity of pembrolizumab in [patients with] Hodgkin lymphoma, microsatellite instability–high tumours, and melanoma.”

Birgit Geoerger, MD, of Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit

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