Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma:an open-label phase 2 trial

Background: The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients. Methods: In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297. Findings: Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment. Interpretation: Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate-fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate-fit patients. Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.</p

Hairy cell leukemia presenting with Ecthyma Gangrenosum- a case report

Abstract Background Ecthyma gangrenosum is a cutaneous infectious usually associated with P. aeruginosa. It usually develops In patients with an underlying immunodeficiency. Case presentation A 50-year old mentally disabled white male with a history of epilepsy presented with fever and a painless red macule on his right arm which rapidly progressed to a painful ulcer. Blood and lesion cultures revealed P.aeruginosa, confirming our clinical diagnosis of ecthyma gangrenosum. Subsequently an underlying immune deficit was found, namely patient was diagnosed with hairy-cell leukemia. Despite adequate antibiotics no infection control could be achieved. After treating the underlying immune deficit as well, the infection and hairy-cell leukemia resolved completely. Conclusion Ecthyma gangrenosum is an important cutaneous infection to recognize, because it is it is typically associated with P.aeruginosa bacteremia. Recognizing this skin leasion should prompt empiric antimicrobial therapy including an agent with antipseudomonal activity. Furthermore, just like in our case, the presence of ecthyma gangrenosum can signal the presence of an occult immune deficit, warranting further investigation

Bridging Anticoagulation in Patients with Atrial Fibrillation

Thrombosis and Hemostasi

Treatment of venous thromboembolism

This review on the treatment of patients with venous thromboembolic disease consists of three sections. The first section describes the epidemiology, natural history and reasons for treatment of venous thromboembolism (VTE), as well as a short overview on the evaluation of the use of antithrombotic agents and the spectrum of treatment options. In the second section, the evidence from clinical studies available to us in 2005 with the various treatment modalities is summarized. This section describes the current recommendations about how to treat patients with WE initially and long term. Finally, in the third section the challenges for the treatment of patients beyond 2005 are discusse

D-Dimer test in cancer patients with suspected acute pulmonary embolism.

Item does not contain fulltextBACKGROUND: The safety of a D-dimer (DD) measurement in cancer patients with clinically suspected pulmonary embolism (PE) is unclear. OBJECTIVES: The aim of this study was to assess the accuracy of the DD test in consecutive patients with clinically suspected PE with and without cancer. METHODS: The diagnostic accuracy of DD (Tinaquant D-dimer) was first retrospectively assessed in an unselected group of patients referred for suspected PE (n = 350). Subsequently, the predictive value of the DD was validated in a group of consecutive inpatients and outpatients with clinically suspected PE prospectively enrolled in a management study (n = 519). The results of the DD test in cancer patients were assessed according to the final diagnosis of PE and the 3-month clinical follow-up. RESULTS: In the first study group, DD showed a sensitivity and a negative predictive value (NPV) of 100% and 100% in patients with cancer and 97% and 98% in those without malignancy, respectively. In the validation cohort, the sensitivity and NPV of DD were both 100% (95% CI 82%-100% and 72%-100%, respectively), whereas in patients without malignancy, the corresponding estimates were 93% (95% CI 87%-98%) and 97% (95% CI, 95%-99%), respectively. The specificity of DD was low in patients with (21%) and without cancer (53%). CONCLUSIONS: A negative DD result safely excludes the diagnosis of PE in patients with cancer. Because of the low specificity, when testing 100 patients with suspected PE, a normal DD concentration safely excludes PE in 15 patients with cancer and in 43 patients without cancer

Diagnostic strategy using a modified clinical decision rule and D-dimer test to rule out pulmonary embolism in elderly in- and outpatients.

Item does not contain fulltextExcluding or confirming pulmonary embolism remains a diagnostic challenge. In elderly patients pulmonary embolism is associated with substantial co-morbidity and mortality, and many elderly patients with suspected pulmonary embolism are inpatients. The safety and efficacy of the combination of a clinical probability (CDR) and d-dimer test in excluding pulmonary embolism in this group is unclear. We retrospectively analysed data of two prospective studies of consecutive in-and outpatients with suspected pulmonary embolism. The patients were categorized into three age groups: 75 years. The sensitivity, negative predictive value and the proportion of patients with the combination of a non-high CDR score according to Wells (75 years) were both 100%. These tests were, however, less reliable for inpatients(n=209), irrespective of their age (sensitivity 91% [ CI: 79-98%], negative predictive value 88 % [CI: 74-96%]. The proportion of both in-and outpatients >75 years with a non-high CDR and a normal d-dimer concentration was only 14%, whereas this was 22% in patients 65-75 years and 41% among in-and outpatients 65 years in which this strategy excludes pulmonary embolism is markedly lower compared to younger patients