Treatment Outcomes of BTK Inhibitors and Venetoclax with/without Anti-CD20 Monoclonal Antibody in Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Real-World Experience

Background: High-risk MCL patients with disease refractory/relapsed (R/R) lack effective treatment options and exhibit poor outcomes, posing challenges in management. The combination of BTK inhibitors (BTKi) and venetoclax obtained high complete remission (CR) and overall response rate (ORR) in clinical trials. The combination data for R/R MCL patients in the real-word is fewer. The aim of the study is to descibe the clinical characteristics and prognosis of BTKi combined venetoclax with or without anti-CD20 antibody in the R/R MCL patients of China.

Methods: A total of 49 patients treated with BTKi and venetoclax 200mg daily (Dual combination, n=17) or in combination with anti-CD20 monoclonal antibody (Triple combination, n=32) between June 2018 and February 2022 at our department were included in this retrospective analysis. All analyses were conducted using statistical language R (version 4.1.2). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results: The median age was 62.0 years and the male-to-female ratio was 3.08:1.Patients had high-risk features including ki67≥30% (89.8%), blastoid/pleomorphic histology (36.7%), high-risk group of MCL International Prognostic Index (MIPI) (42.9%) complex karyotype (27.7%), TP53 mutations (71.4%), TP53 mutations combined with other high-risk gene mutations (57.1%) and 65.3% of progression of disease within 24 months (POD24). The basic clinical characteristics and cytogenetic features in the dual and triple combination were similar. The best ORR and CR were 67.4% and 53.1% in this study, and the 3-year PFS and OS were 37.5% and 50.8%, respectively. Except of TP53 mutations combined with other high-risk genes associating with worse OS, other high-risk factors including high-risk MIPI score, B/PMCL, Ki-67≥50%, POD24, and complex karyotype had the similar efficacy and prognosis to the low-risk. In the MA analysis, SD/PD after combination therapy was independent predictors for PFS and ECOG≥2, TP53 mutations with other high-risk genes mutation and SD/PD after combination treatment were the independent factors for poor OS. The most common adverse reactions were hematological toxicity and pulmonary infection. Finally, the most common death cause was disease progression (19/22) and 7 of them had secondary central nervous system involvement.

Conclusions: The combination of BTKi and venetoclax 200mg daily with or without CD20 antibody had a good efficacy for R/R MCL patients especially in early lines in our study.

No relevant conflicts of interest to declare.