Efficacy of Zanubrutinib Combined with Immunochemotherapy in Newly Diagnosed MYD88-Mutated Diffuse Large B-Cell Lymphoma: A Retrospective Single-Center Study
Authors: Huang Wenrong , Xiao Xiubin , Chen Xilin , Yuan Shunzong , Ma Yi , Zhao Shihua , Lu Yun , Chen Junli , Cheng Nana , Yin Hua , Pan Feng , Wang Yueqi 
Published: December 2024

Background
Diffuse large B-cell lymphoma (DLBCL) patients with MYD88 mutations typically exhibit poor outcomes with conventional first-lineimmunochematherapy of R-CHOP. Zanubrutinib, a Bruton's tyrosine kinase inhibitor, maybe have a promising potential to improve therapeutic responses through MYD88 signaling pathway.
Aims
This single-center retrospective study was designed to evaluate the clinical efficacy of conventional R-CHOP plus Zanubrutinib in DLBCL patients with MYD88 mutations.
Methods
In this retrospective study, we evaluated 20 newly diagnosed DLBCL patients with documented MYD88 mutations by next general sequencing who were treated with Zanubrutinib combined with standard R-CHOP regimen. We analyzed baseline characteristics, therapeutic approaches, and clinical outcomes, encompassing best complete response rate (CRR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Univariate analysis was employed to assess the impact of prognostic factors on treatment outcomes.
Results
A total of 20 patients were analyzed, comprising 17 males (85%) with a mean age of 60.8 years (range: 26-78). Of these, 40% (8/20) were ≤60 years old, and 60% (12/20) were older than 60 years. The majority (85%, 17/20) were classified as non-germinal center B-cell (non-GCB) subtype according to the Hans algorithm. Notably, 40% (8/20) had bulky disease (&gt;5 cm), 40% (8/20) displayed elevated lactic dehydrogenase (LDH) levels, and 45% (9/20) showed B symptoms. Extranodal involvement was very common, affecting 90% (18/20) of the cohort, with 45% (9/20) having two or more sites involved. Regarding the International Prognostic Index (IPI), 35% (7/20) scored 0-1 (low risk), 25% (5/20) scored 2 (low-intermediate risk), 15% (3/20) scored 3 (high-intermediate risk), and 25% (5/20) scored 4-5 (high risk). Half of the patients (10/20) also presented with concurrent CD79B mutations. All participants received Zanubrutinib combined withR-CHOP. Additional treatments included autologous stem cell transplantation (ASCT) for 25% (5/20), radiation therapy for 45% (9/20), and CNS prophylaxis for 25% (5/20). The observed best CR rate was 75% (15/20) (95% CI, 50.9%-91.3%), and ORR was 90% (18/20) (95% CI, 68.3%-98.8%). At a median follow-up of 16 months, PFS was 60.9% (12/20) (95% CI, 41.6%-89.1%), and OS was 76.2% (15/20) (95% CI, 58.1%-99.9%). Univariate analysis demonstrated that none of the assessed factors (age, Ann Arbor stage, IPI, extranodal involvement, LDH levels, CD79B mutation) significantly influenced the complete response rate (p＞0.05). Additionally, these factors did not manifest significant differences in PFS (log-rank P &gt; 0.05 across all stratified factors). Therefore, the addition of Zanubrutinib maybe overcame the poor impact of these commonly recognized adverse prognostic factors.
Conclusion
The integration of Zanubrutinib into standard first-line regimen has shown efficacy in managing newly diagnosed DLBCL patients with MYD88 mutations. These results suggest that Zanubrutinib is a valuable choice for this patient population.