A Scoping Review of Alternative Anticoagulation Strategies for Hemodialysis Patients with a Mechanical Heart Valve.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have high rates of cardiac valvulopathy but can develop contraindications for vitamin K antagonist (VKA) therapy. We explored the evidence for alternative anticoagulation strategies in patients with ESRD with a contraindication for VKA therapy. METHODS: A scoping review was completed, searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Conference abstracts from inception to March 30, 2021. The study population was patients with ESRD who were on VKA therapy and developed a contraindication to VKA therapy use. All data regarding studies, patient characteristics, anticoagulation strategy, and clinical outcomes were summarized. RESULTS: Twenty-three articles met inclusion criteria. These articles included 57 patients. Contraindications to VKA therapy included calcific uremic arteriolopathy (CUA) (n = 55) and warfarin-induced skin necrosis (n = 2). All studies were either case reports or case series. There were 10 anticoagulation strategies identified. Continuation of VKA therapy was associated with increased death and decreased rates of CUA resolution (80.0% and 10.0%, respectively), compared to apixaban (24.0% and 70.8%), subcutaneous (SC) low-molecular-weight heparin (LMWH) (14.3%, 85.7%), and SC unfractionated heparin (0.0%, 100.0%). While only 5 patient cases were reported with mechanical heart valves, SC LMWH use has been reported in this context with good outcomes. CONCLUSIONS: In patients with ESRD who develop a contraindication to VKA therapy, several alternative anticoagulation strategies have been reported with superior outcomes to VKA continuation. While outcomes appear superior to continuation of VKA therapy, more data are required before definitive recommendations can be made for the patient with ESRD and a mechanical heart valve.

A descriptive cost-analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.

BACKGROUND: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data. METHODS: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020). RESULTS: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange. CONCLUSIONS: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens.

Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial.

The MCRN-003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)-free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m2 ), dexamethasone 40 mg and cyclophosphamide 300 mg/m2 was delivered over 28-day cycles. The primary endpoint was overall response after four cycles. Secondary endpoints included toxicity, response depth, PFS and OS. Exploratory endpoints included the impact of cytogenetics, prior therapy exposure and serum free light chain (sFLC) escape; 76 patients were accrued. The ORR was 85% (68% ≥very good partial response [VGPR] and 29% ≥complete response [CR]). The median OS and PFS were 27 and 17 months respectively. High-risk cytogenetics conferred a worse ORR (75% vs. 97%, p = .013) and median OS (18 months vs. NR, p = .002) with a trend toward a worse median PFS (14 vs. 22 months, p = .06). Prior proteasome inhibitor (PI) or lenalidomide did not influence OS or PFS. The sFLC was noted in 15% of patients with a median PFS of 17 months when included as a progression event. The most common ≥ grade 3 non-hematologic adverse events were infectious (40%), vascular (17%) and cardiac (15%). The wKCD is a safe and effective regimen in relapse, especially for patients ineligible for lenalidomide-based therapies.

Hemophagocytic lymphohistiocytosis/cytokine release syndrome secondary to neoadjuvant pembrolizumab for triple-negative breast cancer: a case study.

As indications for immune checkpoint inhibitors for breast cancer continue to expand, rare toxicities will emerge that require careful consideration and multidisciplinary management. We report the case of a 40-year-old female receiving neoadjuvant pembrolizumab and chemotherapy for locally advanced triple-negative breast cancer who developed cytokine release syndrome (CRS)/hemophagocytic lymphohistiocytosis (HLH). CRS/HLH secondary to pembrolizumab are scarcely documented in the literature and, to our knowledge, have never been reported in the context of neoadjuvant treatment for breast cancer.

Management of Multiple Myeloma: A Review for General Practitioners in Oncology.

Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients with MM have a moderate life expectancy, it remains a heterogeneous disease that often requires multiple lines of chemotherapy for durable control and long-term survival. This review outlines current management strategies for both transplant-eligible and transplant-ineligible patients as well as for relapsed and refractory disease. Advances in drug therapies have widened management options and improved survival. In this paper, we also discuss implications for special populations and survivorship care.

Drug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature.

Thrombotic microangiopathy (TMA) is a life-threatening clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and microvascular thrombosis, resulting in ischemia and organ damage. Multiple myeloma (MM) is a neoplasm arising from clonal plasma cells within the bone marrow. The treatment frequently includes multi-agent immunochemotherapy, often with the use of proteasome inhibitors (PIs) such as bortezomib, carfilzomib, or ixazomib. There are increasing reports of TMA in association with PI exposure. This review summarizes the epidemiology, pathogenesis, and diagnosis of PI-related drug-induced TMA. We will outline the definition and diagnosis of TMA and explore an important cause of hemolysis in patients with MM: drug-induced TMA after PI exposure, an increasingly recognized therapeutic complication. This will be emphasized through the description of 3 novel cases of TMA. These illustrative cases occurred after treatment with high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone as part of the MCRN003/MYX1 phase II clinical trial (NCT02597062) in relapsed MM.

Clinical predictors of positive temporal artery biopsy.

OBJECTIVE: We investigated the ability of known clinical signs and symptoms, as well as common laboratory tests, to correctly predict a positive temporal artery biopsy. DESIGN: A prospective cohort study. PARTICIPANTS: Consecutive patients in a tertiary referral centre undergoing temporal artery biopsy. METHODS: Clinical information was collected using a predesigned questionnaire. Pathology results and laboratory information were collected from digital patient records. MAIN OUTCOME MEASURE: The predictive value of clinical signs, symptoms, and laboratory values of a positive temporal artery biopsy. RESULTS: Over a 3-year period, 259 patients were enrolled and 251 patients were analyzed. Sixty-one patients had a positive biopsy. Clinical features most predictive of a positive biopsy were jaw claudication (positive likelihood ratio [LR+] 2.31) and abnormal temporal artery pulse (LR+ 2.62). Receiver operating characteristic curves generated for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelets values showed an area under curve (AUC) value of 0.71, 0.75, and 0.76, respectively. The initiation of steroids decreased the diagnostic utility of the ESR, CRP, and platelets values (AUC = 0.58, 0.61, and 0.63, respectively). CONCLUSIONS: A variety of clinical signs and symptoms were observed in patients referred for a temporal artery biopsy. Clinical signs and symptoms were less accurate in predicting a positive biopsy than laboratory tests. No combination of clinical signs and symptoms tested was able to predict giant cell arteritis with the certainty necessary to justify or withhold long-term steroid therapy.