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: To study if anti-infective prophylaxis with aciclovir and cotrimoxazole is effective in preventing infections in pts. receiving R-CHOP, we compared infections and treatment-related deaths in two prospective DSHNHL trials with different anti-infective strategies. Methods: 61- to 80-year-old pts. in RICOVER-60 study [Pfreundschuh et al; Lancet Oncol 2008; 9:105-116] received 6 or 8 cycles of CHOP-14 with or without 8 applications of rituximab. Anti-infective prophylaxis consisted of ciprofloxazine (500 mg/d) during days of severe leukocytopenia (<1000/mm3). In OPTIMAL > 60, pts. were randomized to 6xCHOP-14 or 6xCHLIP-14 (conventional substituted by liposomal vincristine [2 m/m2, uncapped]) in combination with rituximab, 8 applications q 2 weeks or 12 applications between days -4 and 238 in a 2 × 2 factorial design. In OPTIMAL > 60, anti-infective prophylaxis consisted of cotrimoxazole (2 double-strength doses twice every week p.o.) and aciclovir (4 × 400 mg/d p.o.) in addition to ciprofloxazine. Results: In RICOVER-60, grade 3&4 infections in 232 patients (IPI = 1 and bulky disease or IPI > 1) receiving 6xCHOP-14 + 8R were 6% (76/1200) per cycle and 28% (60/218) per patient. OPTIMAL > 60 pts. were older (70 vs 68 years) and had more IPI = 3 (33% vs 29%) and IPI = 4.5 (34% vs 23%) compared to RICOVER-60. With intensified anti-infective prophylaxis in OPTIMAL > 60, there were no differences with respect to infections between the 4 treatment arms. Despite the considerably less favourable demographics of the OPTIMAL > 60 study, grade 3&4 infections were 4% (83/1987) per cycle and 18% (64/365 pts. with toxicity documentation) per patient, significantly less than in RICOVER-60 (per cycle: p = 0.007; per patient: p = 0.004). Even more importantly, treatment-related deaths (defined as all non-lymphoma associated deaths during and within 2 months after the end of chemotherapy) went down from 15/232 (7%) in RICOVER-60 to 7/385 (2%) in OPTIMAL > 60 (p = 0.003). Conclusion: Anti-infective prophylaxis with cotrimoxazole and aciclovir in addition to ciprofloxazine significantly reduced the rates of severe infections and treatment-related deaths in elderly patients receiving R-CHOP supporting the use of this anti-infective strategy in all DLBCL patients receiving R-CHOP. Keywords: diffuse large B-cell lymphoma (DLBCL); immunochemotherapy; R-CHOP