6808: Leukemia In Medicine:

Many of the 247 medicines in the pipeline are building on novel scientific approaches and looking at new ways to treat blood cancers. Examples of innovative treatments in development include: A second-generation tyrosine kinase inhibitor in development for leukemia may block activation of the FLT-3 cell receptor, which is mutated in about one-third of all patients with acute myeloid leukemia (AML). Activation of this receptor by different types of mutations appears to play an important role in tumor cell proliferation, resistance to programmed cell death, and prevention of normal cell development. Research into new treatments for AML is important, as no new therapies have been approved for 90 percent of AML cases in the last 40 years. Several therapeutic antibodies in development for multiple myeloma target CD38, a protein that is found on the surface of myeloma cells. The therapeutics work by binding to the CD38 protein on the surface of the myeloma cell and then signaling the immune system to attack the cancerous cells. Cutting-edge next generation sequencing has identified a number of genetic mutations that may lead to new treatment options for patients. For example, a medicine in development for advanced hematological malignancies inhibits a mutated form of the IDH2 gene, which encodes a metabolic enzyme. The genetic mutation can lead to increased production of an oncometabolite that prevents immature white cells from developing into healthy infection-fighting cells. The immature white blood cells accumulate and squeeze out normal blood cells and platelets, leading to hematological malignancies, such as leukemia. Through genomic screening, it was found that more than 90 percent of patients with hairy cell leukemia have a mutation in the gene that encodes BRAF kinase. Researchers are now studying an inhibitor of BRAF kinase that is currently approved for the treatment of melanoma. High rates of response, which were achieved early after the onset of therapy, have been observed. A fully human monoclonal antibody in development for Hodgkin lymphoma targets the PD-1 (programmed death-1) checkpoint receptor. This receptor is expressed on T-cells and is part of a normal pathway that inhibits the immune system when needed. Cancer cells may exploit this pathway to protect the tumor from attack by the immune system. Blocking activation of this pathway may allow for immune responses that recognize and destroy cancer cells. Medicines that block the PD-1 receptor have been approved by FDA for the treatment of malignant melanoma and advanced non-small cell lung cancer Partnerships among patient advocates, industry, academia and others are important to moving biopharmaceutical research forward. The Leukemia & Lymphoma Society (LLS) is a leader in driving and supporting research into new medicines and supporting diagnostics through the Therapy Acceleration Program (TAP). TAP helps fund research projects that have the potential to change the standard of care for patients with blood cancers, especially in areas of high unmet medical need. Examples of research projects funded by TAP include: A potential first-in-class DOT1L-targeted histone methyltransferase inhibitor is in development for mixed lineage leukemia (MLL), a devastating genetically-defined type of acute leukemia that affects both pediatric and adult patients. DOT1L is a novel and important epigenetic target. Proteins called histone methyltransferases attach methyl groups to histones, proteins that help package DNA. This histone modification affects gene expression and is a type of change called an epigenetic change. The DOT1L protein is a histone methyltransferase that has been implicated in MLL. A novel targeted therapy in development is an engineered fusion of recombinant interleukin-3 (IL-3) with truncated diphtheria toxin, and is directed to cancer stem cells and tumor bulk. The therapy is in development for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare hematological disorder with high unmet medical need and no standard treatment. The impressive progress made against blood cancers has resulted in more effective treatments that have extended and improved patients’ lives. The 247 medicines in the pipeline today are our best hope for continuing this progress and reducing the burden of blood cancers for generations to come