Primary anti-infective prophylaxis during routine treatment of lymphoma in the United States: A large real-world cohort analysis.

Abstract

268 Background: While infectious complications contribute to considerable morbidity and mortality in patients with cancer, most scenarios lack evidence to guide optimal anti-infective prophylaxis (AIP). We evaluated a large real-world dataset to identify baseline utilization and factors associated with AIP in patients with non-Hodgkin lymphoma (NHL) treated in the US-community setting. Methods: Using the nationwide Flatiron Health de-identified electronic health record-derived database (from ≈ 280 US cancer clinics), we selected patients treated prior to 7/1/2020 with 1) R-CHOP for DLBCL, 2) bendamustine and rituximab (BR) for CLL/SLL, or 3) ibrutinib for CLL/SLL. We limited our analysis to patients treated by providers with documented prescribing of guideline recommended anti-viral prophylaxis (ppx) during proteasome inhibitor administration to ≥1 multiple myeloma patient. Our main outcome was the documented use of primary AIP defined as anti-viral and/or pneumocystis jiroveci (PJP) ppx within +/- 14 days of treatment initiation. We also report the delayed documented AIP use from day 15 to 60. We applied separate multivariable logistic regression models to each setting to examine the associations of patient-level characteristics with primary AIP (including age, sex, race, region, insurance, ECOG, year of treatment initiation). Results: A total of 3,142 (R-CHOP for DLBCL), 2,180 (BR for CLL/SLL), and 3,590 (ibrutinib for CLL/SLL) patients were included, with median age of 69, 69, and 72 years, respectively. Primary AIP was most common during BR for CLL/SLL, with 16.8% receiving any AIP (antiviral 15.6%, PJP 7.3%). Primary AIP was used in 10.5% of DLBCL patients initiating R-CHOP (antiviral 7.6%, PJP 5.6%), with the lowest utilization of AIP during ibrutinib for CLL/SLL (any 6.4%, antiviral 5.6%, PJP 2.6%). In the delayed setting, an additional 4-6% and 2-5% received viral and PJP ppx, respectively. Across all three of our multivariable analyses, higher provider rate of anti-viral ppx during proteosome inhibitor administration in MM, residing in the Midwest (vs. Northeast), and more recent treatment initiation were associated with greater odds of AIP. Other patient characteristics (age, race, ECOG) were less consistently associated with AIP across models. Furthermore, C-statistics were <0.7 in all three models (0.660-0.685), suggesting suboptimal discrimination for AIP based on patient-level characteristics alone. Conclusions: We observed low utilization of primary AIP during treatment in three common NHL settings that lack clear consensus on AIP. Variation was not well explained by measured patient characteristics, and future studies should consider provider and system attributes. Ultimately, robust evidence generation (e.g. pragmatic clinical trials) and quality improvement measures are needed to optimize ppx during routine lymphoma management.