ANTI‐INFECTIVE PROPHYLAXIS WITH ACICLOVIR AND COTRIMOXAZOLE SIGNIFICANTLY REDUCES THE RATE OF INFECTIONS AND THERAPY‐ASSOCIATED DEATHS IN ELDERLY PATIENTS WITH DLBCL UNDERGOING R‐CHOP IMMUNOCHEMOTHERAPY

Abstract

Background: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We investigated the efficacy of dose-dense chemoimmunotherapy and systemic CNS prophylaxis in two completed Nordic trials including patients less than 65 years with high-risk DLBCL. We combined individual patient data from these studies to compare clinical outcome and prognostic factors in patients treated with CNS prophylaxis given in the beginning (CHIC) vs at the end (CRY-04) of therapy.Patients and Methods: Inclusion criteria were age 18-65 years, primary DLBCL or grade 3 follicular lymphoma without signs of CNS involvement, WHO performance score 0-3, age-adjusted International Prognostic Index (aaIPI 2-3) and/or involvement of anatomical sites associated with an increased risk for CNS recurrence (e.g. testis, facial sinuses, orbita). In CRY-04, six courses of R-CHOEP14 were followed by HD-Mtx and HD-Ara-C. In CHIC, treatment consisted of two courses of HD-Mtx in combination with R-CHOP14, followed by four courses of R-CHOEP14 and one course of R-HD-AraC. In addition, liposomal AraC was administered intrathecally at courses 1, 3 and 5.Primary end points were failure free survival (FFS; disease progression, discontinuation of protocolled therapy due to toxicity, death from any cause) at 3 years and CNS progression rate at 1.5 years. Secondary end points included progression-free survival (PFS; disease progression or death from any cause) and overall survival (OS) at 3 years. Conclusions:Our results derived from trial data with homogenous treatment support the use of HD-Mtx in the beginning rather than at the end of therapy. Superior outcome seems to be primarily due to better systemic control of the disease. In addition, number of CNS recurrences is reduced.

Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus

“…Both trials [ 4 , 90 ] identified a high cumulative dose of corticosteroids (cumulative PEQ dose ≥ 2500 mg/m 2 or 3000 mg/m 2 body surface area (BSA)) and a history of neutropenic fever as independent risk factors on multivariate analysis. Whereas these retrospective data only describe incidences of clinical reactivations of herpesviridae , introducing oral acyclovir (400 mg QID given from the start of therapy until four weeks after the last therapy cycle) together with cotrimoxazol (2 double strength doses twice a week) in addition to oral ciprofloxacin (500 mg BID) as anti-infective prophylaxis in the OPTIMAL > 60-trial significantly reduced grade 3/4 infections of all kind (from 28 to 18% per patient, p = 0.004) and treatment-related mortality (from 7 to 2%, p = 0.003) in elderly patients with DLBCL compared to a historical control [ 91 ]. Antiviral prophylaxis was also shown to reduce the risk of clinical reactivations of VZV and HSV in patients with indolent lymphomas treated with bendamustine ± anti-CD20 monoclonal antibody [ 92 ].…”