HBV reactivation is a serious complication of some anticancer therapies. Preliminary studies suggested high rates of HBV reactivation, with fatal outcome, in pts with PCNSL treated with standard HD-MTX-based CT. Risk of HBV reactivation is further increased by the use of Rituximab (Rtx), which significantly improves efficacy of CT in PCNSL. Hence, HBV-positive pts are usually excluded from prospective trials, with a negative effect on accrual, and are treated with less intensive therapies, resulting in lower cure rates. Herein, we report the incidence of HBV infection and reactivation in a mono-institutional series of PCNSLs treated with modern strategies.
HIV-negative pts with newly diagnosed PCNSL treated with CT containing HD-MTX and Ara-C ± rituximab at our Institution, from 2010 to 2016, were analyzed to establish incidence of HBV infection, hepatotoxicity and treatment-related viral reactivation.
48 pts (median age 58, range 29–76) were considered. Eight (17%) pts had “resolved” HBV infection (negative HBsAg but positive anti-surface [anti-HBs] or anti-core [anti-HBc] Antibodies), one (2%) pt had active infection. HBV prophylaxis with lamivudine was indicated in 3/8 pts with resolved HBV. The pt with active infection was treated with entecavir. Induction comprised HD-MTX plus Ara-C in 2 pts, HD-MTX, Ara-C and Rtx in 2, and HD-MTX, Ara-C, thiotepa and Rtx in 5 (MATRix). Transient grade 1-2 elevation of hepatic enzymes (AST, ALT, GGT) was observed in all pts; grade 3-4 was recorded in 17/39 (44%) HBV-negative pts and in 5/9 (56%) HBV-positive pts (Fisher exact; p = 0.71). Eight out of 9 HBV-positive pts received the 4 planned CT courses without dose reductions due to hepatotoxicity; six pts achieved a CR and received consolidation (WBRT 2, ASCT 3, lenalidomide maintenance 1). At a median follow-up of 27 months for the whole series (12-88), no pt experienced HBV reactivation during first-line treatment, 5 pts remain relapse-free.
This study suggests that MTX-Ara-C-based therapy, MATRix regimen, in particular, can be safely used in PCNSL pts with HBV infection, without impaired life expectancy.
Clinical trial identification
Legal entity responsible for the study
IRCCS San Raffaele
All authors have declared no conflicts of interest.