Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center.

Real world effectiveness, toxicity and costs analyses from chimeric antigen receptor (CAR)-T cell therapy are of utmost relevance to determine whether and how to offer patients highly personalized immunotherapy. In this study, we aimed at describing CAR T-cells effectiveness, safety and costs in a Portuguese Comprehensive Cancer Center. We performed a retrospective descriptive study of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed follicular lymphoma referred to CAR T-cell therapy, between May 2019 and February 2021. Rates of treatment response, toxicity and survival (Kaplan-Meier method) were analyzed by intention-to-treat. Direct medical costs stratified by inpatient-care, outpatient-care, and diagnostic-therapeutic procedures (DTP) were derived based on resources used and their respective unit costs. In twenty patients (median age 49.5y; 55%male; 70%DLBCL; 50% with primary refractory disease), best overall and complete response rates were 65.0% and 45.0%, respectively. Median overall (OS) and progression-free survivals were 9.2 and 7.3 months; 12-month OS rate was 42.6% (95%CI:23.2-78.3). Grade≥3 cytokine release syndrome and neurotoxicity occurred in 5.6% and 11.1% of patients, respectively. CAR T-cell therapy expenditure, including adverse events costs, was 7 176 196€, or 286 238€ when excluding drug cost. Median cost for treated patient was 355 165€ with CAR T-cell drug cost accounting for 97.0% of the overall expense. Excluding CAR T-cell acquisition cost, inpatient-care and DTP accounted for 57% and 38% of total cost/patient, respectively. Our findings highlight the heavy economic burden of CAR T-cell therapy driven by drug acquisition costs.

Clinical Characteristics, Treatment and Evolution of Splenic and Nodal Marginal Zone Lymphomas-Retrospective and Multicentric Analysis of Portuguese Centers.

INTRODUCTION: Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome. OBJECTIVES: Describe the clinical characteristics, treatment, outcomes and incidence of HT. METHODS: Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT). RESULTS: This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor. CONCLUSION: Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance.

Withdrawing and Withholding Life Support in Patients With Cancer in an ICU Setting: A 5-Year Experience at a European Cancer Center.

OBJECTIVE: This was an observational retrospective study aimed to examine the frequency and associated factors of withdrawing or withholding life support (WWLS) in the intensive care unit (ICU) of a comprehensive cancer center. METHODS: Medical records of adult patients with cancer admitted to the ICU between January 2010 and December 2014 were reviewed. Patients who died during that period were classified into 2 groups: full life support and withdrawing and withholding life support. The relative impact of demographic and clinical factors was assessed using logistic regression. RESULTS: A total of 247 patients died in our unit (mortality rate of 16.3%). Their median age was 62 (interquartile range [IQR] 51-73) years, there were 142 (57.5%) male patients, and they had predominantly solid malignancies (62.3%). The median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation scores were 67 (IQR 54-80) and 29 (IQR 23-55), respectively. Ninety-six (38.9%) patients died after WWLS with no statistically significant differences in decisions to limit therapy during the study period. Patients with advanced age, solid malignancies, nonneutropenic, and longer duration of mechanical ventilation were more likely to die after WWLS. In multivariate analysis, presenting with neutropenia was independently associated with a lower likelihood of dying after WWLS (odds ratio: 0.34, 95% confidence interval: 0.15-0.80). CONCLUSION: Limitation of therapy has been a common practice in oncologic ICUs over recent years. Neutropenia is an independent predictor of limitation of therapy.