January 16, 2024

In recent years, the treatment of relapsed and refractory mantle cell lymphoma (MCL) has gradually shifted from traditional immunotherapy to a chemotherapy free era, and clinical research on many new molecular targeted drugs is constantly being carried out. The Bcl-2 family proteins are important factors regulating cell apoptosis and are abnormally expressed in most hematological malignancies. The most widely used Bcl-2 inhibitor in clinical practice, Vinaclat, has shown good efficacy in relapsed and refractory MCL, but at the same time, resistance has also emerged in some populations.

Current status of treatment for relapsed and refractory MCL

MCL is a highly heterogeneous disease in biology. Inert MCL patients, due to slow disease progression, can enter clinical observation, and the median time from diagnosis to treatment is generally more than 2 years. The vast majority of MCL patients in clinical practice exhibit invasiveness and treatment should be initiated immediately after diagnosis. The initial response rate of these MCL patients to first-line immunotherapy is 50% to 70%, but the median progression free survival (PFS) period is only 7 to 10 years, and they face the dilemma of disease recurrence and progression in refractory MCL. Therefore, several representative small molecule targeted drugs have begun to be used for the treatment of relapsed and refractory MCL.

Application of Bcl-2 inhibitors in relapsed and refractory MCL

Although the monotherapy of Vinaclera has significant therapeutic effects on MCL, the CR rate is still relatively low. Therefore, exploring the combination of Vinaclera with other treatment options has become a trend. In a phase II clinical trial (NCT02471391) of 24 patients with relapsed and refractory MCL treated with combination therapy of Vinaclat and Ibrutinib, the ORR was 71% and the CR rate was 62% according to PET-CT evaluation after 16 weeks of treatment; The most common AE during the treatment process is gastrointestinal symptoms.

Research on Resistance to MCL Bcl-2 Inhibitors

Although vincla has been applied in the treatment of MCL and has shown significant efficacy, studies have found that some malignant tumor cells with high expression of Bcl-2 protein exhibit significant resistance to vincla, indicating that the expression level of Bcl-2 protein is not the only determinant of cancer cell sensitivity to vincla. At present, the phenomenon of resistance to vinaclar has been studied in some hematological tumors, but its mechanism in MCL is not yet clear. Therefore, revealing the resistance mechanism of vinaclotide in MCL will further provide a basis for subsequent treatment of MCL.

At present, the research and development of multiple drug clinical trials are underway, and the emergence of new small molecule targeted drugs has changed the treatment pattern of relapsed and refractory MCL patients. The Bcl-2 protein is widely expressed in MCL patients and regulates the endogenous apoptosis process of MCL cells. The application of Bcl-2 inhibitors can further improve the remission rate and prognosis of relapsed and refractory MCL patients.

Industry news reference source: Research progress on the treatment of relapsed and refractory mantle cell lymphoma with Bcl-2 inhibitors and their resistance mechanisms