Treatment of Relapsed or Refractory Aggressive B-Cell Lymphomas: Optimization of Combination Therapy with Glofitamab, Gemcitabine, and Oxaliplatin to Minimize Cytokine Release Syndrome

Aggressive B-cell non-Hodgkin lymphomas, such as diffuse large B-cell lymphoma (DLBCL), are fast-growing cancers of the lymphatic system. If the disease recurs after standard therapy (recurrence) or does not respond adequately to treatment (refractory), alternative therapies are used. Glofitamab is a bispecific antibody. It binds simultaneously to tumor cells and to the body’s own immune cells (T cells). This specifically activates the T cells to destroy the cancer cells. However, this activation of the immune system can also trigger an excessive immune response. This is known as cytokine release syndrome (CRS) and can manifest as fever, chills, and a drop in blood pressure, among other symptoms.

The goal of this Phase 2 study is to investigate the combination of glofitamab, gemcitabine, and oxaliplatin (Glofit-GemOx). The focus is on the frequency and severity of CRS. Seven days before the start of combination therapy, patients receive pretreatment with obinutuzumab. The goal of this pretreatment is to reduce the number of B cells and thereby lower the risk of CRS. This is followed by treatment with glofitamab in combination with gemcitabine and oxaliplatin over a total of 8 to 12 cycles, with 21-day intervals between cycles. Maintenance therapy with glofitamab may follow. All medications are administered as intravenous infusions. The study is open-label (not blinded). This means that both the patients and the medical staff know which treatment is being administered. It is a single-arm study, meaning that all patients receive the same treatment and there is no control group. The primary objective of the study is to evaluate safety based on the incidence of CRS. In addition, the efficacy of the therapy, tumor response, and survival will be monitored over a period of up to five years.

Eligible participants include women and men aged 18 and older with aggressive B-cell non-Hodgkin lymphoma. This includes, among others, diffuse large B-cell lymphoma as well as certain highly malignant B-cell lymphomas with genetic alterations. The disease must have recurred after at least one prior course of treatment or must not have responded adequately to that treatment. Patients must have received at least one prior course of treatment and must either be ineligible for high-dose chemotherapy followed by stem cell transplantation or have already undergone such therapy without sufficient success. In addition, at least one measurable tumor lesion must be present.