Optimum Methotrexate Exposure in Patients With Suspected or Confirmed CNS Invasive Hematological Malignancies: A Systematic Critical Review.

BACKGROUND AND METHODS: The present review aims to evaluate the current state-of-the-art dosing regimens of high-dose (HD) and intrathecal methotrexate (MTX) using therapeutic drug monitoring (TDM) to optimize its therapeutic response and minimize associated toxicity, particularly in the central nervous system (CNS). RESULTS: MTX is administered systemically in a HD regimen (>1 g/m 2 ) for the treatment of various hematological neoplasms. HD-MTX treatment becomes complicated by marked interindividual drug elimination variability. TDM is specified to manage this high variability. Approximately 3%-7% of adults with acute lymphoblastic leukemia are diagnosed with CNS involvement, and the incidence of CNS relapse in patients, despite receiving prophylaxis, ranges from 5% to 10%. HD-MTX penetrates the blood-brain barrier and can be administered intrathecally, making this drug an important component of chemotherapy regimens for patients with hematologic malignancies involving the CNS or those at high risk of CNS relapse. CONCLUSIONS: The major evidence found was that an MTX area under the curve target between 1000 and 1100 µmol hour -1 L is associated with better clinical outcomes. However, there seems to be a clinical gap in the prospective validation of HD and IT MTX management to optimize clinical outcomes and minimize toxicity, using the relationship between exposure level (area under the curve MTX) and optimal response to MTX, at systemic and CNS exposure.

Multiple Myeloma in Portugal: Burden of Disease and Cost of Illness.

BACKGROUND: Multiple myeloma (MM) is the second most common hematological cancer worldwide and has significant morbidity and mortality and is increasing in incidence. While MM management costs are considerable, specific economic data at the country level remain scarce. OBJECTIVE: This study assesses the burden and cost of MM in Portugal from the perspective of the National Health Service (NHS) to support the definition of health policies, resource allocation and patient care. METHODS: Developed by the Portuguese Multiple Myeloma Group, this study considers the most recent available data. Burden of disease was measured using disability-adjusted life-years (DALYs). The cost of MM was estimated using a prevalence-based model that estimated direct costs for the NHS considering all costs associated with diagnosis, hospitalizations, surgeries, emergency visits, medical appointments, drugs and transportation. Costs were quantified based on the diagnosis-related group funding price, except for drug usage, which was calculated using the average hospital product stock price. RESULTS: The burden of disease attributable to MM for 2018 was estimated at 8931 DALYs: 8570 resulting from premature deaths and 361 from disability. Average yearly direct costs per patients with MM amounted to €31,449 (year 2018 values). Total direct costs are estimated at €61 million per year. CONCLUSIONS: The mortality rate in MM means that most DALYs are due to years of life lost rather than years lost due to disability. This study generates comprehensive data on the burden and cost of MM in Portugal and provides updated insights into the costs associated with the management of MM.