Bispecific antibody-based frontline therapy for follicular lymphoma
Philippe Armand
PhD, MDDana-Farber Cancer Institute
Project Term: July 1, 2024 - June 30, 2027
We are conducting a clinical trial testing a novel form of immunotherapy, called a bispecific antibody, as part of initial treatment for patients with follicular lymphoma. The goal of the trial is two-fold: 1) to establish a highly effective, chemotherapy-free treatment option for patients with follicular lymphoma, and 2) to establish predictors of response and toxicity that can guide treatment decisions for future patients with follicular lymphoma.
"Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma with approximately 15,000 diagnoses each year in the United States. While outcomes for patients with FL have improved in recent years, the disease remains largely incurable. Currently, chemotherapy makes up the backbone of frontline treatment for most patients, but it is associated with frequent and potentially serious side effects, particularly among elderly patients. Patients with FL would benefit from additional frontline treatment options that provide durable remissions with a favorable safety profile.
Bispecific antibodies (BsAbs) are a novel class of immunotherapy drugs that work by bringing immune cells called T cells in close proximity to lymphoma cells, thereby promoting the killing of the cancer cells by the patient’s own immune system. This class of drugs has shown very promising results in FL and the first BsAb was approved by the US Food and Drug Administration for treatment of relapsed or refractory FL in 2023. Based on these encouraging results, we are conducting a clinical trial of epcoritamab (a BsAb) in combination with rituximab (an antibody drug commonly used to treat FL) in patients with untreated FL. The trial is currently enrolling patients. One of the key potential side effects of BsAbs is cytokine release syndrome (CRS), an inflammatory response that can occur soon after BsAb initiation. In our trial, four doses of rituximab are administered before patients receive the first full dose of epcoritamab with the goal of shrinking the patient’s lymphoma and thereby reducing the risk of CRS. The primary goal of the study is to show that a high percentage of patients can achieve a complete remission at the end of 9 months of study treatment. In addition, patients will complete quality of life surveys periodically during and after study treatment with the hypothesis that BsAb-based treatment will be associated with better patient-reported outcomes than those normally seen with chemotherapy.
Many questions remain about how best to use BsAbs in FL. In our trial, we are collecting serial samples (blood, stool, tumor biopsies) from trial participants with the goal of identifying potential predictors of response and toxicity. We hope to find features that are associated with durable responses with BsAb treatment, which could be used in the future to select patients who are likely to have excellent outcomes without chemotherapy. Similarly, we will look for factors that are associated with a higher risk of CRS, which could be used to guide pre-treatment and patient monitoring during BsAb initiation according to an individual patient’s risk. We expect that our trial could pave the way for a highly effective, well-tolerated, chemotherapy-free front-line regimen for patients with FL. Furthermore, we hope that our scientific studies will identify factors that can guide the use of BsAb treatment for FL patients in the future."