First-line treatment for primary breast diffuse large B-cell lymphoma using immunochemotherapy and central nervous system prophylaxis: A multicenter phase 2 trial

There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.