Abstract
To characterise the effectiveness of Bruton tyrosine kinase inhibitors with venetoclax in patients with refractory or relapsed mantle cell lymphoma, with or without the addition of an anti-CD20 antibody. Progression-free and overall survival were estimated for forty-nine patients treated with Bruton tyrosine kinase inhibitors and venetoclax (200 mg, daily) or in combination with an anti-CD20 monoclonal antibody between June 2018 and February 2022 in China. The median number of treatment lines before combination therapy was three (range, 2-7). The median patient age was 62 years, with a male-to-female ratio of 3.08:1. Patients exhibited high-risk features including Ki-67 ≥ 30% (89.8%), blastoid/pleomorphic histology (36.7%), high-risk mantle cell lymphoma International Prognostic Index group (42.9%), complex karyotype (27.7%), TP53 mutations (71.4%), TP53 mutations combined with other high-risk gene mutations including KMT2D, NSD2, CCND1, NOTCH1, CDKN2A, NOTCH2 and SMARCA4 (57.1%), and progression of disease within 24 months (65.3%), with similar efficacy and prognosis to low-risk cases. Basic clinical and cytogenetic characteristics, as well as efficacy and survival, were similar between the dual and triple combination therapy groups (all p > 0.05). The optimal overall response and complete remission rates were 67.4% and 53.1%, respectively. The 3-year progression-free and overall survival rates were 37.5% and 50.8%, respectively. Eastern Cooperative Oncology Group≥2was an independent predictor of progression-free survival. Eastern Cooperative Oncology Group performance status ≥ 2, TP53 mutations combined with other high-risk gene mutationswere independent factors for poor overall survival. The most common adverse reactions were haematological and pulmonary infections. The leading cause of death was disease progression (19/22). The combination of Bruton tyrosine kinase inhibitors and venetoclax, demonstrated good efficacy in patients with refractory or relapsed mantle cell lymphoma, particularly in the early treatment. There was no efficacy or survival advantages of adding CD20 antibodies. Patients in the ultrahigh-risk group required more aggressive treatments.