Polypharmacy independently predicts survival, hospitalization, and infections in patients with lymphoid cancer

Polypharmacy is a result of multimorbidity and may limit treatment options in patients with lymphoid cancer (LC). To investigate the clinical impact of polypharmacy, we gathered a prediagnostic 1-year medication history from the Danish prescription register for 46,803 newly diagnosed patients with six lymphoma subtypes, chronic lymphocytic leukemia, and multiple myeloma (MM). Medication was grouped into individual drug classes (n = 79), polypharmacy, and the number of prescription medications and correlated with overall survival (OS), hospitalization, and severe infection. Adjusting for age, sex, and multiple testing, we demonstrated associations between 39 drug classes and OS, 29 drug classes and hospitalization, and 27 drug classes and severe infection. Although polypharmacy (<5 vs. ≥5) was associated with adverse outcomes (hazard ratio [HR] 1.4 for OS, hospitalization, and severe infection; P < 0.001), the number of medications (0-3 vs. 4-7 vs. 8-11 vs. >11) gradually stratified OS (HR 1.0 vs. 1.2 vs. 1.4 vs. 1.9, respectively; P < 0.001), hospitalization (HR 1.0 vs. 1.3 vs. 1.4 vs. 1.9, respectively; P < 0.001), and severe infection (HR 1.0 vs. 1.2 vs. 1.5 vs. 1.9, respectively; P < 0.001) in multivariable analyses adjusted for age, sex, comorbidity, and prognostic indices. Lastly, the time to next treatment for Hodgkin lymphoma, mantle cell lymphoma, and MM was gradually shorter with an increasing number of medications (P < 0.001). In conclusion, a 1-year medication history summarized as the number of medications is a strong, independent prognostic and predictive marker that should be considered as a key baseline characteristic in randomized clinical trials and in clinical practice for LC patients.