Routine Prophylaxis of Pneumocystis Pneumonia from the Fourth Cycle of R-CHOP Regimen in DLBCL Patients

Introduction: In our previous report, approximately 10% of diffuse large B cell (DLBCL) patients experienced non-neutropenic fever (NNF) during R-CHOP chemotherapy, and interstitial pneumonitis comprised approximately 55% of NNF cases. Pneumocystis jirovecii is one of the most common pathogens causing interstitial pneumonia, and increasing evidences suggest that R-CHOP may increase the risk of PJP with reported incidence of 5%.

Method: A total of 404 patients with newly diagnosed DLBCL between Jan 2012 and Aug 2016 who were registered in the prospective study and were treated with R-CHOP were analyzed in this study. Before Mar 2014, primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was not performed, whereas, bactrim (1 table daily) was dosed from the initiation of 4th cycle of R-CHOP chemotherapy thereafter. With this change of institutional strategy, we hypothesized that the incidence of PJP may differ by prophylaxis strategy.

Results: The median age was 56 years (range, 20-85) and 297 patients (73.5%) completed 6 cycles of R-CHOP chemotherapy. The rest completed 1 (n=18, 4.5%), 2 (n=4, 1.0%), 3 (n=23, 5.7%), 4 (n=37, 9.2%), 5 (n=14, 3.5%), 7 (n=3, 0.7%) and 8 (n=8, 2.0%) cycles of treatment. Overall, 3 (0.7%) and 9 patients (2.2%) were diagnosed with definite and probable PJP during the period, and the incidence of definite plus probable PJP was 5.4%. Of 404 patients in the cohort, 220 (54.5%) patients were the candidates for routine prophylaxis with Bactrim. The incidence of definite and probable PJP before prophylaxis was 4.9% (9 out of 184 patients), which was decreased to 1.4% (3 out of 220 patients) after routine prophylaxis with bactrim (p=0.038). In the era of prophylaxis, 3 cases of PJP were all occurred before the 4^th cycle and there was no PJP cases after the 4^th cycle, while 6 PJP cases before Mar 2014 were noticed after 4-6 cycles of R-CHOP (0% vs 3.3%, p=0.007).

Conclusion: Routine prophylaxis with bactrim during later cycles of R-CHOP regimen significantly reduces the incidence rate of PJP in DLBCL patients.