This study is the first to compare the efficacy of ibrutinib plus rituximab with standard immunochemotherapy in first-line therapy, demonstrating that the ibrutinib combination significantly prolongs progression-free survival and offers a new treatment option for elderly patients with mantle cell lymphoma.
Literature Overview
The article \"Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH)\" published in The Lancet reviews the comparative efficacy of ibrutinib plus rituximab versus standard immunochemotherapy in patients aged ≥60 years with previously untreated mantle cell lymphoma. The study shows that ibrutinib plus rituximab outperforms traditional immunochemotherapy in progression-free survival with manageable safety profiles, establishing a new treatment standard for elderly patients.
Background Knowledge
Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma characterized by chromosomal translocation t(11;14)(q13;q32), leading to dysregulated cell cycle control and tumor proliferation. MCL typically presents as aggressive, with most patients diagnosed at advanced stages. Current treatment strategies include immunochemotherapy (e.g., R-CHOP or rituximab plus bendamustine) followed by rituximab maintenance therapy, yet most patients experience recurrence or progression. As a Bruton tyrosine kinase (BTK) inhibitor, ibrutinib blocks B-cell receptor signaling and has demonstrated superiority over traditional immunochemotherapy in second-line treatment. However, its efficacy in first-line therapy remains unconfirmed by randomized controlled trials. The ENRICH study addresses this gap by evaluating the efficacy and safety of ibrutinib plus rituximab versus standard immunochemotherapy in elderly patients with untreated MCL. The study employs a multicenter, open-label, randomized design with progression-free survival as the primary endpoint, providing evidence for future MCL treatment strategies.
Research Methods and Experiments
The ENRICH trial is an international multicenter, open-label, randomized phase 2/3 study enrolling previously untreated MCL patients aged ≥60 years with Ann-Arbor stages II-IV and ECOG performance status 0-2. Patients were randomly assigned 1:1 to receive either ibrutinib plus rituximab or standard immunochemotherapy (R-CHOP or bendamustine plus rituximab), followed by two-year rituximab maintenance therapy. The primary endpoint was investigator-assessed progression-free survival, with secondary endpoints including overall survival, objective response rate, safety, and quality of life.
Key Conclusions and Perspectives
Research Significance and Prospects
The ENRICH study provides the first randomized evidence demonstrating the significant progression-free survival advantage of ibrutinib plus rituximab, particularly against R-CHOP, suggesting its potential as a new standard for elderly MCL patients. Future research should explore efficacy in specific subgroups (e.g., TP53 mutations, Ki67 high expression) and assess overall survival benefits through long-term follow-up. Optimizing treatment duration and combining with other targeted therapies (e.g., BCL-2 inhibitors or CAR-T) may further enhance outcomes.
Conclusion
The ENRICH study provides critical evidence for MCL treatment, demonstrating superior progression-free survival with ibrutinib plus rituximab compared to traditional immunochemotherapy, particularly in R-CHOP-controlled comparisons. Although overall survival showed no significant difference, the chemotherapy-free approach exhibited better tolerability and quality of life in elderly patients. This research strongly supports ibrutinib plus rituximab as a new first-line treatment standard and lays the foundation for optimizing BTK inhibitor-based combination therapies.
