Clinical Outcomes of Breast-Involved Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Real-World Study with Insights into CNS Prophylaxis

This study evaluated clinical characteristics, treatment outcomes, and CNS relapse patterns in patients with breast-involved diffuse large B-cell lymphoma (DLBCL), a rare extranodal presentation with limited real-world data. We conducted a retrospective study on 33 consecutive patients with newly diagnosed breast-involved DLBCL treated from 2019 to 2024. All patients received R-CHOP. Baseline CNS screening—including neurological examination, fundoscopy, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis—was routinely performed. High-dose methotrexate (HD-MTX) was offered as CNS prophylaxis after completion of systemic therapy based on multidisciplinary team evaluation and clinician–patient shared decision-making according to institutional treatment protocols. Median age was 52.6 years; 84.8% had ECOG 0. Non-GCB subtype predominated (84.8%), and Ki-67 >70% was present in 69.7%. The overall response rate was 90.9%, with 84.8% complete responses. At a median follow-up of 44 months, 5-year Overall Survival (OS) and Progression-Free Survival (PFS) were 84.8% and 66.7%. CNS relapse occurred in 4 of 6 patients (66.7%) without prophylaxis, all within 5–11 months after R-CHOP, whereas no CNS relapses were observed among prophylaxis recipients (p < 0.001), although this observation should be interpreted with extreme caution given the very small non-prophylaxis subgroup (n = 6), limited statistical power, and non-randomized treatment allocation. Exploratory analyses suggested that bulky disease was associated with inferior OS. R-CHOP achieved high response rates and favorable long-term outcomes in breast-involved DLBCL. The absence of CNS relapse among HD-MTX prophylaxis recipients, contrasted with a high relapse rate in those without prophylaxis, provides only a hypothesis-generating observation that requires confirmation in larger prospective studies; this warrants further investigation of the role of systemic CNS prophylaxis.