Yasmin H. Karimi, MD, on Diffuse Large B-Cell Lymphoma: Update on Use of Epcoritamab Plus Chemotherapy

For patients with relapsed refractory diffused large B-cell lymphoma salvage chemo-immunotherapy followed by consolidation with high-dose chemotherapy and autologous stem cell transplant is potentially curative, but 40 to 60% of patients can't proceed to a stem cell transplant generally due to an insufficient response to chemo-immunotherapy, and outcomes are particularly poor for patients with primary refractory disease or those with early relapse or sero rates are as low as 7%. ZUMA seven trial did show an overall survival benefit to second-line CAR T-cell; however, many patients are not candidates for CAR T or face barriers to treatment, including the distance away from a tertiary care medical center, barriers to treatment including distance away, comorbidities or rapid disease progression. And there's a need for better treatment options. Epcoritamab is a subcutaneously administered CD3, CD20 bispecific antibody and has been approved for the treatment of adults with relapsed refractory large B-cell lymphoma after two or more lines of systemic therapy and has been shown to be safe and effective in combination with standard treatments including Rituximab and chemotherapies. This is a phase two trial evaluating the combination of Epco plus R-DHAX in patients with transplant eligible, relapsed, or refractory diffused large B-cell lymphoma. The primary objective of the escalation part was the rate of dose-limiting toxicity and safety and tolerability. The primary endpoint of the expansion was overall response rate. In the expansion cohort, Epcoritamab was given until high dose chemotherapy and ontological stem cell transplant or until disease progression. As of January 2024, twenty-nine patients had received treatment. The median age was 58 and most patients had primary refractory disease or had progressed within 12 months of initial therapy. With a median follow-up time of 27.7 months, 55% of patients had proceeded to stem cell transplant. Median [inaudible 00:01:58] of dose intensity was high. Response rates were high overall, as well as in high risk subgroups with an overall response rate of 71%, and a CR rate of 63% in patients with primary refractory disease or relapse within 12 months of initial therapy. Median time to response and complete response is 1.4 and 1.5 months, respectively, in the overall population. With 27 months of median follow-up, complete responses were durable, including among high risk patients who received autologous stem cell transplant. An estimated 60% of patients including high risk patients were progression free at 24 months. All of the high risk patients who received autologous stem cell transplant all were progression free at 24 months, and Kaplan-Meier curves show that most patients, including high risk patients were alive at 24 months. Patients who proceeded to a stem cell transplant had durable remissions and five patients continued into upgraded to have monotherapy instead of transplant, two of whom had durable responses and remain on therapy beyond 30 months. The most common treatment emergent adverse events were hematologic toxicity and treatment emergent adverse events that led to R-DHAX dose modification, and discontinuation occurred in 11 and 3% of three patients, respectively. One patient had ICANN, which was grade two and resolved. Clinical tumor lysis syndrome did not occur, and there were no fatal treatment emergent adverse events. CRS was low grade occurring in 45% of patients, all grade one to two with no grade three or higher cytokine release syndrome and most commonly occurred on day 15 after the first full dose of treatment. No CRS events led to Epcoritamab discontinuation. In conclusion, with longer follow-up and new high-risk subgroup analyses, the efficacy and feasibility of Epcoritamab with R-DHAX, an auto-eligible DLBCL, support further exploration of this regimen for patients who are unable to proceed to CAR T or various to CAR T access.