Orelabrutinib with or without Anti-CD20 Monoclonal Antibodies Is Highly Effective and Well Tolerated As First-Line Therapy for Marginal Zone B Cell Lymphoma
Authors: Yao Na , Li Xin , Yang Jing , Cong Jia , Wang Liang 
Published: December 2024

Background:
Marginal zone B cell lymphoma (MZL) is the most common type of indolent lymphoma in China. No standard-of-care regimens have been defined yet for first-line therapy in patients with MZL. Chemo-free regimens, such as rituximab plus lenalidomide, have been used increasingly in elderly patients. Orelabrutinib, a new-generation bruton's tyrosine kinase (BTK) inhibitor, was approved by National Medical Products Administration (NMPA) in 2020 to treat chronic lymphocytic leukemia and mantle cell lymphoma. Then in 2023, orelabrutinib was approved by NMPA to treat relapsed/refractory MZL. In this retrospective study, we aimed to explore the efficacy and safety of orelabrutinib combined with or without anti-CD20 monoclonal antibodies as first-line therapy for a consecutive cohort of patients with MZL.
Methods:
33 consecutive MZL patients with indications for treatment received orelabrutinib with or without rituximab or obinutuzumab as first-line therapy during the past three years in Beijing Tongren Hospital. Orelabrutinib was given at the dosage of 150mg once a day continuously. Rituximab was given at the dosage of 375mg/㎡body square, once a cycle, which repeated every 21 days, to a total of 4-6 cycles. Obinutuzumab was given at the dosage of 1000mg/㎡ body square, once a cycle to a total of 4-6 cycles. For early stage extranodal MZL, radiotherapy (RT) was also recommended as consolidation therapy with a dosage of 4-24 Grays. For patients with high baseline tumor burden, orelabrutinib monotherapy was administrated as maintenance for 6-12 months. PET-CT, CT, or MRI scan was used to evaluate the efficacy every two cycles. This study was approved by the Ethics Committee of Beijing Tongren Hospital with the approval certificate No. TREC2022-KY103.
Results:
33 patients with newly diagnosed MZL were included in this analysis, with a median age of 61 years old (26-76). The male to female ratio was two. 27 patients were diagnosed as extranodal MALT lymphoma (23 with ocular adnexal; 2 with thyroid; 2 with glottis or maxillary sinus), four patients were diagnosed as nodal MZL, and the remaining two patients were diagnosed as splenic MZL. Using Ann-Arbor staging system, 21 patients had stage I disease, three patients had stage II disease, and the remaining nine patients had advanced disease. All but two patients had recurrent fever as B symptoms, and both patients had elevated level of LDH. According to MALT-IPI score, 23 patients had low-risk disease, and four patients were defined as high-risk. All patients received recommended dosage of orelabrutinib continuously, among whom seven patients were treated with RT as consolidation therapy, 11 patients received obinutuzumab, and another 11 patients received rituximab, and the remaining four patients were treated with orelabrutinib monotherapy. After 4-6 cycles of induction therapy, 10 patients were given orelabrutinib as maintenance therapy. At a median follow-up time of 330 days (35-855), the best overall response rate (ORR) was 100%, and complete response rate (CRR) was 54.5%. Only one patient had disease progression after discontinuation of induction therapy due to economic issues. The median progression-free survival and overall survival were not reached yet. Orelabrutinib-based therapy was well tolerated in the first-line setting of MZL. Concerning the safety profiles, only two patients developed ≥grade 3 neutropenia, and one patient had ≥grade 3 thrombocytopenia. Two patients had transient liver dysfunction. One patient suffered from atrial fibrillation, resulting in discontinuation of orelabrutinib. All side effects were recovered after supportive care. No patients died of MZL or side effects.
Conclusions:
Our retrospective study revealed that orelabrutinib with or without anti-CD20 monoclonal antibodies was highly effective and well tolerated as first-line therapy for marginal zone B cell lymphoma, which needs to be verified in prospective clinical trials.