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 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, 7patients 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).Conclusions: Definitive assessment of the primary endpoint will need longer follow-up. Thus far, comparison of these results with those of the IELSG10 trial (5-yr PFS, 88 vs 74%; 5-yr OS, 92 vs 85%; 5-yr CNS relapse rate, 0 vs 6%) suggests that combined treatment of PTL with R-CHOP21 plus intensive CNS prophylaxis and loco-regional RT is feasible, may abrogate CNS relapses and lead to very promising outcomes. Nevertheless, late relapses, mainly at extranodal sites, still represent a clinical challenge.The research was funded by: Mundipharma provided the drug depocyte free of charge