Primary Breast Double-hit Lymphoma Management and Outcomes: A Real-world Multicentre Experience

Abstract Background: Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnoses and selecting optimal treatment regimens. Methods: We retrospectively reviewed cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results: In total, 48 patients were enrolled, and the overall five-year OS and PFS rates were 41.7% (95% confidence interval [CI], 22.4–64.7%) and 37.5% (95% CI, 23.7–58.6%), respectively. Of the three treatment regimens, the five-year OS was higher in the dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R)/alternating with high-dose methotrexate and cytarabine (MA) group than in the DA-EPOCH-R or rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with cytarabine plus methotrexate (R-HyperCVAD) subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the five-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.038). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (five-year OS: 72.2% vs. 23.3%; P < 0.001; five-year PFS: 72.2% vs. 16.7%, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. Conclusions: DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for relapse reduction. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.