Objective: Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding modalities of treatment to guide the management of AMNs. Methods and Review Criteria: We conducted a PubMed search in February 2016 for English-language publications, using the terms “appendiceal,” “appendix,” “carcinoma,” “cancer,” “mucinous,” “treatment,” “genes,” “target,” “genomic,” and terms listed in the articles' subheadings. Published reports and abstracts from the American Society of Clinical Oncology meetings were also searched. Results: In this review, we summarize current data and controversies in AMN classification, clinical presentation, molecular alterations, treatment outcomes with regard to cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and the role of systemic chemotherapy. Conclusion: Appendiceal mucinous neoplasms are a heterogeneous group of tumors with a rising incidence. Treatment is based on stage and histology. Low-grade tumors are treated surgically with resection of the primary site in early stage disease, or peritoneal debulking and HIPEC in patients with advanced stage disease. Treatment of high-grade tumors requires further prospective trials, and options include debulking surgery and HIPEC with or without preoperative chemotherapy. Trials evaluating novel therapies based on the molecular profiling of AMN tumors are needed to evaluate therapeutic options in patients who are not surgical candidates.

BACKGROUND: Indisulam possesses anticancer properties through down‐regulation of various cell‐cycle checkpoint molecules, thereby blocking the phosphorylation of retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with nucleoside analogs and topoisomerase inhibitors.METHODS: The authors designed a phase 2 study of indisulam in combination with idarubicin and cytarabine in patients who had relapsed/refractory acute myeloid leukemia AML and high‐risk myelodysplastic syndrome. In stage 1, patients received intravenous indisulam at 400 mg/m² on days 1 and 8 of a 28‐day cycle. If they had no response, then patients received same dose schedule of indisulam followed by intravenous idarubicin 8 mg/m² daily for 3 days and cytarabine 1.0 g/m² over 24 hours daily on days 9 through 12 (for those aged < 60 years) or days 9 through 11 (for those aged > 60 years) of a 28‐day cycle. Primary endpoints included the overall response rate, and secondary objectives included overall survival.RESULTS: Forty patients were enrolled. Of the 37 evaluable patients, 31 received indisulam with chemotherapy. Of these, 11 (35%) responded for a median duration of 5.3 months. The estimated 1‐year overall survival rate was 51% for responders compared with 8 % for nonresponders (P < .001). The most common grade ≥3 nonhematologic toxicities were electrolyte abnormalities (50%) and febrile neutropenia (28%).CONCLUSIONS: The combination of indisulam with idarubicin and cytarabine yielded a 35% response rate in heavily pretreated patients with AML. With emerging data identifying the expression of DCAF15 (DDB1 and CUL4‐associated factor 15) as a potential biomarker for activity, the combination of indisulam with idarubicin and cytarabine should be studied in a biomarker‐driven trial or in patients who have splicing factor mutations. Cancer 2018;124:2758‐65. © 2018 American Cancer Society. Cancer 2018;124:2758‐2765. © 2018 American Cancer Society

Purpose of review: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). Recent findings: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML. Monoclonal antibodies in AML therapy include naked antibodies against AML surface antigens such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti-CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive particles such as ¹³¹I or ²²⁵Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and others. Approaches to harness the body's own T cells against AML include antibodies that recruit and induce cytotoxicity of tumor cells by T cells (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab, avelumab) on T cells, unleashing the patients’ T cells against leukemic cells. Summary: The ongoing trials and well designed correlative interrogation of the immune system in patients treated on such trials will further enhance our understanding and clinical application of immune therapies as single-agent and combination approaches for the treatment of AML.