Background: Prescription drug out-of-pocket (OOP) costs remain a major source of financial toxicity in hematology/oncology (heme/onc). Mark Cuban Cost Plus Drug Company (MCCPDC) sells generic drugs directly to patients, bypassing insurance. The purchase cost is equal to drug cost (manufacturing cost, 15% markup, $3 pharmacy fee) and $5 shipping fee. Research shows MCCPDC provides potential savings for Medicare beneficiaries, but its benefit for the commercially insured remains unknown. We assess OOP savings if the eight MCCPDC drugs with heme/onc indications were purchased directly from MCCPDC instead of commercial insurance. Methods: MCCPDC purchase costs were matched with equivalent drugs claims in IBM Marketscan (2021) based on name, strength, formulation, and amount dispensed, using claims with the most frequent days’ supply. Potential OOP savings were calculated by subtracting insurance claim OOP costs (copay + coinsurance + deductible) from MCCPDC purchase cost. Outcomes included % claims with cost savings and amount saved. Savings were calculated for brand-name drugs for which a MCCPDC generic may often be appropriately substituted. Results: Of 145,403 claims, 6.8-24.5% of generic antineoplastics approved post-1990 in MCCPDC and 26% of deferasirox claims would have OOP savings if purchased through MCCPDC, with median savings $63-$561 (Table). 14.8% of brand-name 2nd generation antiandrogen claims would save switching to abiraterone, with median (IQR) saving of $1045 (345, 2010). 43.2% of brand-name 1st/2ndgeneration BCR/ABL tyrosine kinase inhibitors (TKI) claims would save switching to imatinib, with median (IQR) saving of $116 (31, 1286). The share of newer generic antineoplastic claims with savings varied by insurance: high deductible health plan (HDHP) (28.1%), health maintenance organization (HMO) (23.5%), and preferred provider organization (PPO) (13.2%) (p<0.001). Conclusions: Some patients can save hundreds or thousands of dollars per fill by purchasing heme/onc drugs through MCCPDC instead of commercial insurance, with greater savings for HDHP/HMO and from brand-name antineoplastics to appropriately substitutable generics. MCCPDC is a new avenue to decrease financial toxicity.