Current status of immune checkpoint inhibitors in treatment of non-small cell lung cancer.

Lung cancer remains a leading cause of cancer mortality worldwide, including in Korea. Systemic therapy including platinum-based chemotherapy and targeted therapy should be provided to patients with stage IV non-small cell lung cancer (NSCLC). Applications of targeted therapy, such as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and anaplastic lymphoma kinase (ALK) inhibitors, in patients with NSCLC and an EGFR mutation or ALK gene rearrangement has enabled dramatic improvements in efficacy and tolerability. Despite advances in research and a better understanding of the molecular pathways of NSCLC, few effective therapeutic options are available for most patients with NSCLC without druggable targets, especially for patients with squamous cell NSCLC. Immune checkpoint inhibitors such as anti-cytotoxic T lymphocyte antigen-4 or anti-programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have demonstrated durable response rates across a broad range of solid tumors, including NSCLC, which has revolutionized the treatment of solid tumors. Here, we review the current status and future approaches of immune checkpoint inhibitors that are being investigated for NSCLC with a focus on pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab.

An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL).

Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression. MPAL typically carries a worse prognosis than either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). Given the rarity of MPAL, there is a lack of prospective trial data to guide therapy; treatment generally relies on ALL-like regimens followed by consolidation chemotherapy or hematopoietic stem cell transplant (HSCT). Here, we review the updated classification, biology, clinical features, and treatment approach to MPAL.

Advances in therapies for acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia (AML), results from the arrest of the maturation of hematopoietic progenitors at the promyelocyte stage. It has been shown that APL is associated with a reciprocal chromosomal translocation, involving chromosomes 15 and 17, which fuses the gene encoding the retinoic acid receptor α (RARα) and the promyelocytic leukemia (PML) gene. The resultant PML-RARα fusion protein plays a critical role in the pathogenesis of APL. Although there are many subtypes of AML, all are typically managed using a standard chemotherapy regimen of an anthracycline plus cytarabine arabinoside (CA). Despite high rates of complete remission following standard chemotherapy, most patients relapse and long-term disease-free survival is only 30-40%. The introduction of drugs such as all-trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML-RARα fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. The purposes of the present review are to provide the latest results and future directions of clinical research into APL and to illustrate how new therapies, such as ATRA plus anthracycline-based induction and consolidation therapy, risk-adapted therapy, salvage therapy containing arsenic trioxide-based regimens, and hematopoietic stem cell transplantation, have improved the treatment outcomes for APL patients.