Impact of Polypharmacy Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Older Adults: Polypharmacy in Allogeneic Transplantation

Abstract Background : Polypharmacy is common in older adults with cancer but there is little evidence evaluating the impact of polypharmacy and other medication hazards on allogeneic hematopoietic cell transplantation (alloHCT) outcomes. A small number of prior studies have evaluated the impact of potentially inappropriate medication (PIM) use in the setting of alloHCT, with mixed results. Objectives We evaluated the effects of pre-alloHCT polypharmacy, PIM use, and drug-drug interactions (DDI) on post-alloHCT outcomes including overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), hospital length of stay (LOS), number of nonhematologic grade ≥3 adverse events (AE) within 100 days after alloHCT and number of readmissions within the first 100 days after alloHCT. Study Design : The study population was a single-center prospective cohort of 148 patients aged ≥50 years. Pre-alloHCT medication lists were retrospectively collected from the electronic medical record, including both scheduled and as-needed medications. PIM were defined by a modified 2019 American Geriatrics Society Beers Criteria®. DDI were analyzed using Lexi-Interact®. Results : Polypharmacy was common in this population; the median number of medications was 7 (range 0-23). Fifty-two patients (35%) were prescribed 9 or more medications, and 73 patients (49%) had at least one PIM prescribed. The median number of DDI was 3 (range 0-31) and the most common severity was major (48%). After adjusting for age and Hematopoietic Cell Transplant Comorbidity Index (HCTCI), both the number of all medications and number of scheduled medications were associated with inferior OS, with hazard ratio (HR) 1.07 (95% confidence interval [CI], 1.01-1.12; p=0.02) and 1.08 (95% CI, 1.00-1.15; p=0.04), respectively. Receipt of ≥9 scheduled medications was associated with inferior OS (HR 1.92; 95% CI, 1.11-3.32; p=0.02). Number of PIM was also significantly associated with OS, with HR 1.24 (95% CI 1.00-1.54, p=0.05). After adjusting for age, HCTCI, and total number of medications, a greater number of DDI was significantly associated with longer hospital length of stay (difference 0.74 days; 95% CI 0.09-1.40, p=0.03). In adjusted analyses, there were no significant polypharmacy-related predictors of NRM, LOS or non-hematologic grade ≥3 AE. Conclusions : These data demonstrate the utility of pre-alloHCT polypharmacy, PIM use and DDI as important prognostic factors and support routine pre-alloHCT medication review by physicians and pharmacists with a goal of appropriate de-prescribing where possible.