Zanubrutinib in the Treatment of Recurrent Refractory Mantle Cell Lymphoma

Overview

80% of patients with mantle cell lymphoma (mantle cell lymphoma, MCL)were in the advanced tumor stage when they were first diagnosed. Zabutinib, as a new generation of BTK inhibitors, has better targeting and safety in clinical application. Previous studies have confirmed that zabutinib has good efficacy in treating relapsed refractory MCL. However, for patients with a high risk of drug resistance to BTK inhibitors or patients with drug resistance, the efficacy of BTK inhibitors alone is poor, and combined therapy can improve the poor prognosis of these patients. Therefore, the primary purpose of this study is to evaluate the safety and efficacy of zebutenil in treating recurrent, refractory mantle cell lymphoma.

Mantle cell lymphoma (mantle cell lymphoma, MCL) is a kind of B-cell lymphoma with unique histomorphology, immunophenotype, and cytogenetic characteristics, accounting for 6% of non-Hodgkin's lymphoma. It usually occurs in older adults, with a median age of 68. In recent years, although the application of new drugs has made much progress in the treatment of mantle cell lymphoma, the overall curative effect is not good. The vast majority of patients relapse after treatment. The median survival time is 3-5 years due to a lack of standard treatment. MCL responds to combined therapy, but easy recurrence is still problematic in clinical treatment. 50% to 60% of MCL eventually relapsed after treatment. Among them, BTK inhibitors exert their anti-tumor activity by promoting apoptosis and inhibiting tumor cell proliferation, inhibiting chemokine from blocking B cell migration, and reducing tumor B cell adhesion, which has become a milestone in the treatment of recurrent, refractory MCL. Zabutinib, as a second-generation BTK inhibitor, optimizes its chemical structure. Compared with the first-generation BTK inhibitor, zabutinib has complete and lasting BTK inhibition, more accurate targeting selection, and better clinical application safety. Previous clinical studies have shown that BTK inhibitor zabutinib is effective in treating recurrent and refractory MCL. However, using BTK inhibitors alone to produce drug resistance will cause rapid tumor growth in MCL patients, which has always been a difficulty in clinical treatment. A retrospective analysis of 693 Chinese patients with MCL showed that the complete remission rate (CR） of the initial treatment of MCL in China was 40.9%, the objective remission rate（ORR） was 81.6%, the 5-year progression-free survival rate(PFS) was 51.2%, and the 5-year overall survival time (OS) was 58.4%. It is significantly lower than the curative effect on foreign patients. At the same time, 56.8% of the patients relapsed after remission, so the treatment plan for patients in the Chinese population needs to be further optimized. Currently, the clinical application of zabutinib combined with ortozumab, a BCL-2 inhibitor, dexamethasone, and pomalidomide is one of the therapeutic regimens for recurrent refractory MCL with a high complete remission rate and safety. In order to better collect the clinical data on zabutinib combination therapy and make a more scientific and accurate evaluation, this study carried out a clinical observation study on the safety and efficacy of zabutinib combination therapy in recurrent refractory MCL. The survival index was evaluated by the objective remission rate (ORR) of 2 and 4 cycles of the combination regimen, and the adverse reactions and recurrence rates were collected.