The paradigm of early phase studies in hematological malignancies

Hematological Malignancies are at the forefront of rapid advances in molecular technology which has enabled the understanding of the biology and brought us to the cutting edge of diagnosis and therapy. Today, it is possible to routinely sequence the entire genome of patients with blood cancers, providing us with a panorama of the genomic changes that underlie these malignancies. These advances have undoubtedly revolutionized how we diagnose and treat patients with these diseases and other cancers as well. While we understand the pathogenesis of these malignancies in the context of newer therapies, the general approach to diagnosis and treatment are very different in various leukemias, lymphomas, and myeloma. Moreover, the course of the natural history of these various entities is varied; however, the overall goal of treatment is the prolongation of survival and ultimate cure. In this review, we provide a detailed look at the various drugs that have changed the course of treatment of the major types of hematologic malignancies. We discuss a few "gems" in clinical studies that have provided both initial proofs-of-concept and informative testing ground for a variety of targeted/immune-based therapeutics. The key points covered in this chapter include: 1. Early phase clinical trials and evolution of molecular-based assays 2. Phase 1 studies and understanding the biology of the disease 3. Goals of treatment 4. Challenges in designing clinical trial protocols in hematological malignancies 5. Role of biomarkers and bioimaging; approval of new drugs 6. Future studies on the horizon.