Background: Improvements in treatment options for multiple myeloma (MM) have led to double-digit increases in 5-year survival rates over the past 40 years. Such extended survival has increased emphasis for the management of comorbid chronic conditions. Initial analyses suggest that oral anticancer agent (OAA) initiation for MM may correspond to significant reductions in adherence to chronic disease medications. Methods: This was a retrospective cohort study of adults diagnosed with and being treated for MM between 2013-2018 using data from the IBM MarketScan Commercial Claims and Encounters databases and a 20% sample of Medicare claims data. Adults (18 years and older) were included if they were diagnosed with and had at least two claims for an OAA indicated for MM, had continuous enrollment for 12 months both before and after OAA initiation, and were previously diagnosed with two chronic conditions and had prescription fills for select chronic conditions. Medication adherence was determined using the proportion of days covered (PDC) metric and was compared for the 12 months before and after the OAA initiation by Wilcoxon signed-rank tests, McNemar’s tests, and difference-in-differences (DinD) models. Results: A slight majority of the 2,765 patients (total N from both databases) were male (52.3%), and hypertension (94.5%) and hyperlipidemia (69.2%) were the most common comorbid conditions. Mean OAA adherence in the first year of therapy was 55.8% (SD: 23.5) and 63.5% (SD: 26.9) for commercial and Medicare patients, respectively. PDCs for comorbid therapies declined in the first year after OAA initiation, irrespective of payer (table), and the proportion adherent to these therapies (PDC > 80%) also declined consistently. OAA adherence tended to align with the direction of changes in comorbid therapy adherence with those nonadherent to their OAA (PDC < 80%) demonstrating general declines in comorbid therapy PDCs post-OAA initiation (p<0.05 in 4 of 6 DinD models). Conclusions: Among adults with MM and multiple chronic conditions, the pre-OAA initiation level of adherence appears to dictate chronic disease medication use patterns after OAA initiation. The starting of OAA therapy facilitates an opportunity for providers to reinforce the need for total regimen adherence to improve the odds of positive cancer- and non-cancer-related outcomes.