Unveiling Immediate Pseudo-Progression with Epcoritamab in Lymphoma Treatment: Case Series Exploration

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype in the United States, with around 40% of patients experiencing relapse or resistance to initial chemoimmunotherapy. Despite attempts to improve outcomes with treatments like autologous hematopoietic stem cell transplant (AHCT) or CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, fewer than half achieve lasting remission. The recent FDA approval of CD20/CD3 BiTE therapies, such as Epcoritamab, has brought hope to heavily pretreated DLBCL cases. These therapies have shown promising, sustained responses with manageable safety profiles. However, it's important to note that common side effects following Epcoritamab administration. In this context, we present a case series characterized by immediate pseudo-progression of disease with Epcoritamab injection.Case 1: A 49-year-old man initially responded to R-CHOP therapy but experienced disease progression. Epcoritamab treatment led to grade 2 cytokine release syndrome and significant neck mass progression. Flexible laryngoscopy showed left posterior pharyngeal wall protrusion due to mass effect. A neck CT scan showed significant progression of neck mass within left thyroid bed, there was mass effect on trachea, esophagus and larynx (Image A). The patient had a tracheostomy placed and received radiation to left neck mass. The patient had dramatic response. Treatment is planned to resume after radiation.Case 2: A 78-year-old woman with follicular lymphoma had multiple prior therapies. Epcoritamab therapy was initiated. The patient experienced grade 2 CRS, which was managed symptomatically. She also developed significant increasing lymph nodes siz. Despite these side effects, the patient continued Epcoritamab therapy. During her last clinic visit, her lymphadenopathy had completely resolved. Discussion Epcoritamab triggers a strong immune response by engaging both B and T lymphocytes simultaneously. This response leads to beneficial effects like killing cancer cells and releasing proinflammatory cytokines. However, it can also cause complications, including cytokine release syndrome. Some patients experience a phenomenon called tumor flare before responding to treatment, as seen in the EPCORE NHL-1 trial (about 10% of patients) and in a study of another similar therapy, Glofitamab (7% of patients). The report's main goal is to highlight the importance of promptly identifying and managing tumor flare cases during Epcoritamab therapy. To avoid misinterpretation of clinical findings, assessing treatment response should consider a time frame of at least one month after Epcoritamab injection. Vigilant monitoring and timely intervention are crucial to optimize treatment outcomes while addressing immune-related challenges. Further research is needed to understand why tumor flare occurs differently in various patient populations.