A new phase 2 clinical study reveals promising efficacy and safety results for Brukinsa (zanubrutinib) in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for patients with double-expressor lymphoma (DEL).
Clinical Efficacy and Survival Outcomes
The multicenter, prospective, single-arm trial enrolled 48 newly diagnosed DEL patients between November 2020 and July 2022. After a median follow-up of 29.3 months, the combination therapy demonstrated impressive results with an objective response rate of 89.6% and a complete response rate of 83.3%. Two-year progression-free survival reached 81.25%, while overall survival stood at 93.75%.
Of the study population, 31 patients (64.6%) maintained complete response, while 12 patients (25%) experienced progressive disease. Three patients died due to disease progression after six treatment cycles, one from cardiovascular disease, and one from COVID-19 infection.
Molecular Insights and Prognostic Factors
Next-generation sequencing analysis of 33 patients identified TP53, MYD88, and PIM1 as the most frequently mutated genes. Multivariate analysis revealed that BCL-6 gene rearrangement significantly impacted both progression-free survival and overall survival, with a 75.3% and 94.3% lower risk, respectively. The number of extranodal involvements emerged as a significant factor affecting overall survival, with a 15.12 times higher risk.
Treatment Protocol and Safety Profile
The treatment regimen consisted of Brukinsa (160mg twice daily) for six months, combined with a standard R-CHOP protocol administered in 21-day cycles for six to eight cycles. The R-CHOP components included rituximab (375 mg/m²), cyclophosphamide (750 mg/m²), doxorubicin (50 mg/m²), vincristine (1.4 mg/m²), and prednisone (100 mg).
Safety analysis revealed grade 3 adverse events in 23 patients (47.9%). The most common severe side effects included:
- Neutropenia: 18 patients (37.5%)
- Pulmonary infection: 11 patients (22.9%)
- Febrile neutropenia: 3 patients (6.3%)
- Anemia: 4 patients (8.3%)
- Thrombocytopenia: 4 patients (8.3%)
Notably, the treatment was well-tolerated with no dose reductions or interruptions required, particularly benefiting patients 60 years and older who had not shown improvement with ibrutinib R-CHOP in the previous Phoenix study.
Future Directions
The encouraging results have prompted researchers to initiate a multicenter phase 3 clinical study. Investigators are currently exploring the underlying mechanisms of Bruton tyrosine kinase inhibition in DEL and examining additional prognostic factors that may influence treatment outcomes.
