The following is a summary of “A phase 2 study of frontline pembrolizumab in follicular lymphoma,” published in the October 2024 issue of Hematology by Ho et al.     

The tumor microenvironment (TME), including infiltrating T-cells, plays a significant role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to the varied disease course.    

Researchers conducted a prospective study evaluating the efficacy of pembrolizumab as an initial treatment for indolent B-cell lymphoma.    

They enrolled adults with FL or marginal zone lymphoma (MZL) requiring treatment. Patients received 200 mg of pembrolizumab intravenously (IV) in 21-day cycles for up to 18 cycles until progression or unacceptable toxicity. Early response was assessed after cycle 3 with computed tomography (CT), and fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-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.    

The results showed 9 patients with FL (February 2019 and April 2021), including 8(89%) with advanced stage, 7(78%) with intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI), and 6(67%) with high tumor burden by Groupe d’Etude des Lymphomes Folliculaires (GELF). The best overall response rate by FDG-PET-CT was 33% (3 partial metabolic responses), 3 patients (33%) had stable disease, and 3(33%) had progressive disease, including 1 patient who only had a follow-up CT. By CT, 4(44%) experienced a reduction in target lesions, but all were less than partial responses. Grade 3 or higher immune-related adverse events (IRAEs) were observed in 2(22%) patients, both with transaminitis and 1 of these also 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.    

They concluded that frontline pembrolizumab for FL was associated with limited responses and a clinically significant rate of IRAEs. Alternative strategies for targeting the TME in FL should be explored, offering hope for improved treatments in the future.  

Source: onlinelibrary.wiley.com/doi/full/10.1002/jha2.1029