{"doi":"10.1002/jha2.1029","title":"A phase 2 study of frontline pembrolizumab in follicular lymphoma","abstract":"Background: The tumor microenvironment (TME), including infiltrating T-cells, is thought to play a major role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to its widely varied disease course. We hypothesized that programmed death-1 inhibition may be most effective in untreated, immunocompetent FL patients. Thus, we developed a phase 2 study to evaluate the efficacy of pembrolizumab as the initial treatment for indolent B-cell lymphoma. Methods: Adults with FL or marginal zone lymphoma and an indication for treatment were eligible. Patients received pembrolizumab 200 mg IV in 21-day cycles for up to 18 cycles, until progression or unacceptable toxicity. Early response assessment was obtained after cycle 3 with computed tomography (CT), and a fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) was obtained after cycle 6 to determine candidacy for continuation in the study. Immunosecretome profiling was performed at baseline and on cycle 2 day 1. Results: Nine patients with FL were enrolled between February 2019 and April 2021, including eight (89%) with advanced stage, seven (78%) with intermediate/high Follicular Lymphoma International Prognostic Index, and six (67%) with high-tumor burden by Groupe d'Etude des Lymphomes Folliculaires. The best overall response rate by FDG PET-CT was 33% (three partial metabolic responses). Three patients (33%) had stable disease, and three (33%) had progressive disease (including one patient who only had a follow-up CT). By CT four (44%) experienced a reduction in target lesions, but all were less than partial responses. Grade 3 or higher immune-related adverse events (IRAEs) were seen in two (22%) patients, both with transaminitis and one of whom had concurrent hypophysitis. Another patient had grade 1 pneumonitis, requiring treatment with steroids. No associations between the immunosecretome profile and clinical outcomes could be detected. Conclusion: Frontline pembrolizumab for FL is associated with limited responses and a clinically significant rate of IRAEs. Alternative strategies for targeting the TME in FL should be explored.","journal":"eJHaem","year":2024,"id":504549,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":309330,"name":"Songli Zhu","orcid":"0000-0001-8560-5444","position":1,"is_corresponding":false},{"id":236737,"name":"Ted Gooley","orcid":"0000-0002-8182-3652","position":2,"is_corresponding":false},{"id":375811,"name":"Taranjit S. Gujral","orcid":"0000-0002-4453-3031","position":3,"is_corresponding":false},{"id":382922,"name":"Ryan C. Lynch","orcid":"0000-0001-6703-0894","position":4,"is_corresponding":false},{"id":385852,"name":"Christina Poh","orcid":"0000-0003-3120-712X","position":5,"is_corresponding":false},{"id":233391,"name":"Mazyar Shadman","orcid":"0000-0002-3365-6562","position":6,"is_corresponding":false},{"id":643209,"name":"Stephen D. Smith","orcid":"0000-0002-9028-8372","position":7,"is_corresponding":false},{"id":494363,"name":"Yolanda D. Tseng","orcid":"0000-0002-4070-346X","position":8,"is_corresponding":false},{"id":522228,"name":"Ajay K. Gopal","orcid":"0000-0003-3023-6834","position":9,"is_corresponding":false},{"id":1087820,"name":"Carrie Ho","orcid":"0000-0003-4437-9377","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:10:39.578471Z","pmid":"39691260","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}