A recent interim analysis of the phase III ECHELON-3 trial revealed that a triplet combination of brentuximab vedotin (BV), lenalidomide, and rituximab showed a significant improvement in overall survival for patients with diffuse large B-cell lymphoma (DLBCL). The study, conducted by Jeong-A Kim, MD, at the American Society of Clinical Oncology meeting, demonstrated a 37% reduction in the risk of death when BV was added to the lenalidomide-rituximab regimen. This promising outcome addresses a high unmet need for patients with relapsed/refractory DLBCL.
In addition to improved overall survival, the triplet combination also showed enhanced progression-free survival and overall response rates compared to the lenalidomide-rituximab alone regimen. Patients experienced a longer median duration of response and a higher complete response rate when treated with the triplet combination. These results suggest that BV plus lenalidomide-rituximab could be a beneficial treatment option for patients ineligible for other aggressive therapies like CAR-T, transplant, or bispecific antibodies.
Although CAR T-cell therapy and HSCT are powerful treatment options for relapsed/refractory DLBCL, they come with various challenges such as patient factors, disease-related issues, and logistical obstacles. Moreover, the response rates to CAR-T therapy can be suboptimal, with a significant number of patients facing treatment failure. The triplet regimen in the ECHELON-3 trial demonstrated responses in both CD30-positive and CD30-negative disease, offering a potential benefit to high-risk patient subsets like those with a high International Prognostic Index score, older age, or prior exposure to CAR-T therapy.
Despite the positive outcomes observed with the triplet combination, it is important to note the presence of treatment-related adverse events. The trial reported a higher incidence of grade 3 or greater adverse events, including a heightened burden of hematologic toxicity and peripheral neuropathy. Additionally, there were some fatalities related to adverse events, primarily due to neurotoxicity and infections caused by bone marrow suppression, including complications from COVID-19.
The patient population included in the trial reflected real-world clinical practice, with a median age ranging from 70-74 and a diverse demographic representation. Most patients had primary refractory disease, non-germinal center B-cell phenotype, and a high IPI score, indicating a poor prognosis. Prior treatments for the participants included multiple lines of therapy, anthracyclines, anti-CD20 antibodies, CAR T-cell therapy, bispecific antibodies, and HSCT. The results showed a favorable response to the triplet regimen in both CD30-positive and CD30-negative subgroups, with improved response rates and durations of response compared to the lenalidomide-rituximab alone regimen.
Overall, the triplet combination of BV, lenalidomide, and rituximab represents a promising therapeutic approach for patients with relapsed/refractory DLBCL, particularly for those who are ineligible for other aggressive treatments. While the regimen showed substantial benefits in terms of survival outcomes and response rates, it is crucial to consider the associated toxicities and carefully monitor patients for adverse events during treatment. Further research and long-term follow-up studies are needed to confirm the efficacy and safety of this combination therapy in improving outcomes for patients with DLBCL.