Review of Targeted Therapy for Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a type of aggressive lymphoma that can vary in its course, ranging from slow-growing cases that may not require treatment for many years, to highly aggressive cases with a poor prognosis. Two important prognostic factors, regardless of the specific clinical presentation, are the rate of cell proliferation and the expression of the p53 protein. Understanding the biological processes that lead to the development and progression of MCL, as well as the intricate interactions between different components involved in B-cell signaling, has led to the identification of several potential therapeutic targets for MCL. These include molecules that regulate the Bruton's tyrosine kinase (BTK) signaling pathway, which plays a crucial role in B-cell maturation and immune function. The FDA has approved several BTK inhibitors, such as Ibrutinib and Zanubrutinib, for use in treating MCL patients. These drugs work by blocking the activity of BTK, which can help slow down the growth and spread of MCL cells. Acalabrutinib is another BTK inhibitor that is currently under investigation for the treatment of MCL. In the analysis of Acalabrutinib treatment for 124 patients, the median durations of response, progression-free survival (PFS), and overall survival (OS) were 28.6, 22, and 59.2 months, respectively. This was after a median follow-up of 38.1 months. These results are longer than those reported in the combined analysis of Ibrutinib. When analyzing the treatment with Ibrutinib for 370 patients with relapsed or refractory MCL, the median durations were 21.8, 12.5, and 26.7 months for response, PFS, and OS, respectively. The median follow-up time was up to 41.4 months. Similarly, in a combined analysis of Zanubrutinib treatment for relapsed or refractory MCL in 112 patients, the medians were 24.9, 25.8, and 38.2 months for response, PFS, and OS. The median follow-up was 24.9 months. We would like to emphasize that the proportion of patients with blastoid or pleomorphic histology was 12% (44 patients) in the Ibrutinib group and 13% (140 patients) in the Zanubrutinib group. ORR (80.8%) was observed in patients with blastoid/pleomorphic morphology who were treated with Acalabrutinib, Ibrutinib, and Zanubrutinib. These results confirm the long-term efficacy and safety of BTK inhibitor therapy in the treatment of relapsed/refractory MCL.