INTENSIFIED (INTRAVENOUS AND INTRATHECAL) CNS PROPHYLAXIS IN PRIMARY TESTICULAR DIFFUSE LARGE B‐CELL LYMPHOMA: 5‐YEAR RESULTS OF THE IELSG30 TRIAL

Abstract

Introduction: Primary diffuse large B-cell lymphoma of the testis (PTL) represents a unique condition characterized by high long-term risk of contralateral testis and central nervous system (CNS) relapse (>30% at 15 years) in historical series (Zucca et al, JCO 2002). Immunochemotherapy associated with intrathecal CNS prophylaxis and contralateral testis radiotherapy (RT) improved patient outcome, with a virtual elimination of contralateral recurrences and significant reduction (6% at 5 years) of CNS relapses in the IELSG10 trial (Vitolo et al., JCO 2011). The International Extranodal Lymphoma Study Group (IELSG), in cooperation with the Italian Lymphoma Foundation (FIL), coordinated the multicenter phase II IELSG30 study to assess activity and feasibility of intensified CNS prophylaxis in combination with chemoimmunotherapy and RT. Patients and Methods: Patients with stage I-II PTL were eligible. Treatment consisted of 6 cycles of the standard R-CHOP21 regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone every 21 days); 4 doses of intrathecal liposomal cytarabine; 2 courses of intravenous (iv) intermediate-dose methotrexate (1.5 gr/m2) and RT (25-30 Gy) to the contralateral testis. The study was designed to demonstrate (80% power, a = .05) a PFS improvement from 67% to 82% at 10 years (primary endpoint). Results: Fifty-four patients (median age: 66 years, range: 37-79 years) with untreated stage I (n = 32) or II (n = 22) PTL were treated with R-CHOP21, 53 received at least 3 doses of intrathecal CNS prophylaxis, 48 received at least one dose of iv methotrexate and 50 received prophylactic RT. No unexpected side effects were observed. At a median follow-up of 5 years, 7 patients progressed and 7 died, with 5-year PFS of 88% (95%CI, 74-94%) and 5-year OS of 92% (95%CI, 79%-97%). No CNS relapses occurred. In 4 cases, both nodal and extranodal relapses were reported, the latter including the gastrointestinal tract and the pleurae in the same patient, as well as, 1 patient each, the kidneys, the spinal canal (extra-axial) and the contralateral testis (9 years after RT). Two patients relapsed only at extranodal sites (skin, adrenal gland), 1 had nodal relapse. Notably, 4 of 7 failures were late relapses occurring after 6 to 10 years from treatment. Causes of death were lymphoma (n = 4), second cancer (n = 1), cerebral vasculopathy (n = 1), unknown (n = 1). The research was funded by: Mundipharma provided the drug depocyte free of charge Keywords: Combination Therapies, Radiation Therapy Conflicts of interests pertinent to the abstract A. J. M. Ferreri Consultant or advisory role: Adienne - Gilead - Novartis - Juno - PletixaPharm Research funding: BMS - Beigene - Pharmacyclics - Hutchison - Medipharma - Amgen - Genmab - ADC - Therapeutics - Gilead - Novartis - Pfizer E. Zucca Consultant or advisory role: Beigene - Celgene - Incyte - Janssen - Merck - Roche - Celltrion Healthcare - Kite (Gilead) Research funding: AstraZeneca - Celgene - Incyte - Janssen - Merck - Roche Educational grants: Roche – Abbvie