HIGH-DOSE WEEKLY CARFILZOMIB, CYCLOPHOSPHAMIDE, AND DEXAMETHASONE IN THE TREATMENT OF PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA – EXPLORING THE FINANCIAL COST AND RARE SIDE-EFFECTS

Abstract

Multiple myeloma Multiple myeloma (MM) is a malignant disorder of clonal plasma cells based in the bone marrow that leads to devastating symptoms including renal failure, hypercalcemia, anemia, and fractures. Treatment efficacy has improved due to the advent of new therapies; however, there is also an increase in toxicity and cost (1,2). MYX.1 Trial The MYX.1 clinical trial is a single arm phase II multi-centre trial that explored the efficacy of high-dose weekly carfilzomib with cyclophosphamide and dexamethasone (wKCD) for relapsed MM. The trial met its primary endpoint with a high overall response rate (84%) (3) Life-threatening Drug Side-effects Cases of thrombotic microangiopathy (TMA), a rare but life-threatening syndrome of microangiopathic haemolytic anaemia, thrombocytopenia, and multi-organ dysfunction, have been reported in patients receiving carfilzomib (4–8). Herein, I will determine the incidence, clinical phenotype, and predictive factors associated with TMA and carfilzomib based on the MYX.1 trial data. Cost of Myeloma Therapy In Canada, MM represents 1.5% of cancer diagnoses but up to 20% of some provincial oncology drug budgets (G. Mitera, personal communication, March 30, 2020). MM is not curable, and treatment is continuous until the time of disease progression. This study determines the cost of high-dose wKCD, from the perspective of the payer, based on MYX.1 trial data. Results A high rate of TMA (4%) was seen in patients treated in the MYX.1 clinical trial. The management of carfilzomib related DITMA should focus on supportive care and cessation of carfilzomib. Based on the MYX.1 trial data, the mean total cost of high-dose weekly KCD was $203,336.08 CAD per patient (pt). The predominant cost driver was chemotherapy at $179,332.78/pt where the cost of carfilzomib was $162,471.65/pt. The cost of carfilzomib is minimized through this high-dose once weekly KCD dosing schedule. We calculated the cost of biweekly carfilzomib at $300,576.70/pt (compared to $179,332.78 per patient on wKCD), a potential cost savings of $104,663.43/pt from direct drug costs and $16,580.49/pt from drug administration costs. Conclusions High-dose wKCD is an active triplet regimen for RRMM associated with reduced total cost compared with twice weekly regimens and its toxicity is provisionally acceptable.