IELSG30 phase 2 trial: intravenous and intrathecal CNS prophylaxis in primary testicular diffuse large B-cell lymphoma.

Primary testicular diffuse large B-cell lymphoma (PTL) is characterized by high-risk of contralateral testis and central nervous system (CNS) relapse. Chemoimmunotherapy with intrathecal (IT) CNS prophylaxis and contralateral testis irradiation eliminates contralateral recurrences and reduces the CNS relapses. The IELSG30 phase II study (ClinicalTrials.gov NCT00945724) investigated feasibility and activity of an intensified IT and intravenous (IV) CNS prophylaxis. Untreated patients with stage I-II PTL received 2 cycles of IV high-dose methotrexate (MTX) (1.5 gr/m2) after 6 cycles of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone every 21 days). IT liposomal cytarabine was administered on day 0 of cycles 2 to 5 of R-CHOP21. Contralateral testis radiotherapy (25-30 Gy) was recommended. Fifty-four patients (median age: 66 years) with stage I (n=32) or II (n=22) were treated with R-CHOP, 53 received at least 3 doses of IT cytarabine, 48 received at least one dose of IV MTX and 50 prophylactic RT. No unexpected toxicity occurred. At a median follow-up of 6 years, there was no CNS relapse; 7 patients progressed and 8 died, with 5-year progression-free and overall survival rates of 91% (95%CI, 79-96%) and 92% (95%CI, 81%-97%), respectively. Extranodal recurrence was documented in 6 patients (in 2 without nodal involvement). In 4 cases the relapse occurred more than 6 years after treatment. Causes of death were lymphoma (n=4), second primary malignancy (n=1), cerebral vasculopathy (n=1), unknown (n=2). Intensive prophylaxis was feasible and effective in preventing CNS relapses. Late relapses, mainly at extranodal sites, represented the most relevant pattern of failure.