Multiple Myeloma (MM) is a deadly blood cancer that has 30,000 new diagnoses each year. In 2022, the market for treating this cancer is expected to grow to $21B. This market is dominated by drugs whose efficacies are limited by their toxicity. Through chemical design, we invented a novel macromolecular prodrug platform that vastly improves the leading MM drug therapeutics ranging from proteasome inhibitors to immunomodulators. In our proof of concept work, we have created pharmaceuticals with over 25-fold improved therapeutic indexes and more than 3-fold increased life expectancies when compared to treatments currently used in the clinic.