The role of ibrutinib in COVID-19 hyperinflammation: A case report.

Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD). Given their potential to suppress pulmonary inflammatory cytokines and lessen acute lung injury, this could be applicable in the context of hospitalised COVID-19 patients. We describe an 81 year-old male receiving ibrutinib for Waldenstrom macroglobulinaemia (WM) who was hospitalised with COVID-19. On stopping the BTKi due to concerns of additional immunosuppression, he required non-invasive ventilation (NIV) in the intensive care unit (ICU) and demonstrated prompt clinical recovery when ibrutinib was reinstated. Continuing ibrutinib in patients with COVID-19 may be advantageous given its immunomodulatory properties and withdrawal of ibrutinib therapy may be detrimental. Further evidence is required to explore the potential therapeutic impact of BTKis and other immunomodulatory agents on the clinical course of COVID-19 as is currently being carried out in a number of clinical trials.

Efficacy and tolerability of peptide receptor radionuclide therapy (PRRT) in advanced metastatic bronchial neuroendocrine tumours (NETs).

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) has been proven to be effective in gastro-entero-pancreatic neuroendocrine tumours (NETs) using 90Yttrium (90Y)- or 177Lutetium (177Lu)-based somatostatin peptides, with 177Lu-DOTATATE recently licensed. There is less published evidence of PRRT in metastatic bronchial NETs. OBJECTIVE: The aim of this study was to evaluate the efficacy, safety and toxicity of PRRT in patients with bronchial NETs, to expand the evidence base in this rare type of tumour. MATERIALS AND METHODS: This was a retrospective analysis of all patients with moderate to well-differentiated typical or atypical bronchial NETs treated at the Royal Free Hospital Nuclear Medicine Department with at least two cycles of 90Y-DOTA-OCTREOTATE and/or 177Lu-DOTA-OCTREOTATE between 2009 and 2020. Response rates, progression free survival (PFS), overall survival and toxicity were evaluated. Factors associated with treatment response were evaluated. RESULTS: Of the 25 patients with bronchial NETs treated with PRRT in our department between 2009-2020, 7 (28 %) had 90Y-DOTATATE and 18 (72 %) had 177Lu-DOTATATE. 44 % of patients had PRRT as third, fourth of fifth line treatment. 72 % of patients had liver metastases and 76 % skeletal metastases at baseline. Median progression-free survival (PFS) was 17 months (177Lu-DOTATATE = 18 months; 90Y-DOTATATE = 12 months) and the median overall survival was 42 months. High proliferation rate (ki-67 > 20) and low somatostatin receptor (SSR) uptake (score of 2) were associated with shorter PFS. CONCLUSION: PRRT appears to be a safe treatment in somatostatin receptor positive bronchial NETs, even in patients who have been heavily pre-treated. The efficacy of PRRT is comparable with if not favourable to other systemic therapeutic options.

Hyponatraemia in patients with multiple myeloma.

Hyponatraemia is the most common electrolyte disturbance encountered in clinical practice. Several causes of hyponatraemia are recognised and in many patients the aetiology may be multifactorial. An important cause is water intoxication and this is often iatrogenic. We present three patients, all of whom suffered from multiple myeloma, who illustrate different aspects of hyponatraemia, its causes and management.

Role of interferon-alpha in patients with neuroendocrine tumors: a retrospective study.

BACKGROUND/AIM: Interferon alpha (IFNα) is used sparingly in the management of neuroendocrine tumors (NETs) due to toxicity and perceived limited efficacy. Other medical therapeutic options include somatostatin analogues and molecular-targeted agents, as well as chemotherapy and radionuclide targeted-therapy. The aim of the present study was to perform a retrospective analysis of patients treated with IFNα. PATIENTS AND METHODS: Patients were identified from the NET database. Radiological, biochemical and symptomatic response were assessed. Progression-free survival (PFS), adverse events and toxicities were recorded. RESULTS: Thirty-five patients were treated with IFNα, with a mean age of 60.1 (range=38-85) years; eight patients (23%) withdrew before 3 months, one (3%) had complete response; there was one partial response; 25 patients (71%) had at least three months of stable disease. The median PFS was 25 months. CONCLUSION: IFNα demonstrated efficacy and was reasonably tolerated. IFNα may still have a role in small-volume diffuse disease, in syndromic patients where there is resistance to somatostatin analogue, or as a bridge to other therapies.