Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial.

All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with the primary objective of exploring the safety and tolerability of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing the relevant antigen, folate receptor-alpha. The trial incorporated skin prick and basophil activation tests (BAT) to select patients at lowest risk of allergic toxicity. Secondary objectives were exploration of anti-tumour activity, recommended Phase II dose, and pharmacokinetics. Dose escalation ranged from 70 µg-12 mg. The most common toxicity of MOv18 IgE is transient urticaria. A single patient experienced anaphylaxis, likely explained by detection of circulating basophils at baseline that could be activated by MOv18 IgE. The BAT assay was used to avoid enrolling further patients with reactive basophils. The safety profile is tolerable and maximum tolerated dose has not been reached, with evidence of anti-tumour activity observed in a patient with ovarian cancer. These results demonstrate the potential of IgE therapy for cancer.

Therapeutic strategies for chemotherapy-induced neutropenia in patients with solid tumors.

INTRODUCTION: Chemotherapy-induced neutropenia (CIN) is a common adverse event during treatment of cancer patients, associated with increased morbidity, mortality, health care costs and impairment of patients' quality of life which necessitate dose reductions. AREAS COVERED: A computerized systematic literature search was performed through Medline, PubMed, Google Scholar and the Cochrane Library to identify peer reviewed publications relevant to CIN, pathophysiology and epidemiology, patient risk-assessment and existing treatment approaches. Additionally, emerging issues such as alternative therapeutic options and implications in elderly care were addressed. EXPERT OPINION: Although CIN represents a common adverse event in the management of patients with solid tumors, the heterogeneity in clinical practice across different settings underlines the need to improve existing tools for accurate patient classification. Moreover, the definition of the optimal implementation of out-patient treatment and the use of colony-stimulating factor as add-on treatment together with antibiotics should be further investigated in order to accumulate more solid data. Finally, physician education is required to ensure that scientific knowledge is implemented in the daily clinical practice.

A case of herpes simplex-associated encephalitis after brain irradiation for lung cancer metastases.

BACKGROUND: Encephalitis caused by Herpes Simplex Virus-1 is a devastating disease with high mortality and disability rates despite adequate treatment. No clear risk factors have been identified although iatrogenic immunosuppression has been suggested, among others. CASE REPORT: A 59-year-old male smoker was diagnosed with metastatic lung adenocarcinoma and was treated with brain and spinal irradiation. Ten days after the completion of radiotherapy and before initiating platinum-based front-line chemotherapy, he developed low grade fever and personality change. Over the next few days, high fever and refractory seizures developed and the patient was diagnosed with Herpes simplex-associated encephalitis after detection of viral DNA in the cerebrospinal fluid via polymerase chain reaction. Despite treatment with acyclovir, the patient remained comatose and died three months after the initial presentation. CONCLUSION: This case illustrates a possible association between brain irradiation and increased risk for Herpes simplex-associated encephalitis. However, the underlying mechanisms have not been elucidated.