Predictive Factors of Response to Immunotherapy in Lymphomas: A Multicentre Clinical Data Warehouse Study (PRONOSTIM).

Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.

[Causes of medication administration errors in elderly people: a systematic review]. / Causes des erreurs médicamenteuses à l'administration chez la personne âgée : une revue de la littérature.

The elderly are particularly vulnerable to medication administration errors (MAE). To prevent these errors, it is crucial to identify and understand their causes. A review of the literature using the PRISMA method was conducted. Of 2,798 articles, 15 were included in the literature review. The causes identified were divided into 4 categories: patient-related, direct drug-related, healthcare professional-related, and organizational, teamwork, and environmental causes. It was found that the causes were many and varied (n = 56). These were mostly related to physical and cognitive disorders of the patient. Few studies of causes based on empirical data were conducted on this specific subject. The majority of studies were conducted in a health care facility and institution. Therefore, this study cannot provide a comprehensive review of all the risk factors for MAE, especially in the elderly who are capable of administering their medication on their own. To study this topic, a complementary literature review on the causes of non-adherence in the elderly would be necessary.

Performance evaluation of the HPLC diode array and evaporative light scattering detection for the implementation of dose-banded gemcitabine infusion bags.

BACKGROUND: Dose banding (DB) was used to optimise the individualisation of patient treatments with gemcitabine (Gem) in order to improve workload planning at the pharmacy of the University Hospital Centre of Besançon (UHCB). A new simple and fast high-performance liquid chromatographic (HPLC) method was also developed for the quantification of Gem without dilution of the infusion bags. METHODS: Individual doses of Gem preparations were retrospectively analysed over a 1-year period to determine the frequency of prepared doses. Using a maximum gap of 7.5% around the doses chosen, the selected Gem standard doses were 1400 mg, 1600 mg, 1800 mg and 2000 mg. Following the DB scheme, the frequency of prescription of standard and individualised Gem doses was analysed over a period of 10 months. The four selected Gem standard doses were aseptically prepared in polyolefin infusion bags. Each series of 20 bags was stocked under refrigerated storage conditions (4°C) for up to 84 days. The quantification of Gem without dilution of the infusion bags was obtained by the development of a HPLC method coupled to a diode array detector (DAD) or an evaporative light scattering detector (ELSD). RESULTS: During the 10-month period following implementation of the DB, 75.6% of the 1266 prescribed doses were covered by the four standardised preparations. The number of different Gem doses was reduced from 183 to 55. Concerning the Gem quantification, both heteroscedasticity and non-linearity were observed with DAD. Using an ELSD, the trueness values were between 98.59% and 101.52% with excellent repeatability values between 0.66% and 1.42%. CONCLUSION: A new HPLC method has been developed for the quantification of Gem without dilution of the infusion bags prepared in advance as a result of a target DB scheme successfully implemented in our pharmacy department.

Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study.

PURPOSE: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year. RESULTS: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders (P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders (P = .005), respectively. CONCLUSION: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

Impact of pharmacist medication review for paediatric patients: an observational study.

BACKGROUND: Paediatric patients are at high risk of medication errors and adverse drug events due to complex medical care. OBJECTIVE: To assess the impact of pharmacist medication review for paediatric patients. SETTING: A single-centre prospective observational study was performed over 33 months, from February 2018 to October 2020 in a French Hospital. METHOD: Clinical pharmacists provided medication counselling at a hospital and conducted telephone follow-ups between 3 and 7 days after discharge of paediatric patients with chronic diseases for whom treatment was introduced or modified during hospitalisation or hospital consultations. MAIN OUTCOME MEASURES: The incidence of drug-related problems (DRPs), the number and type of pharmacist intervention and paediatrician acceptance rates were assessed. Parents' understanding and drug-related needs were compared before and after medication review. Time to outpatient treatment and patient satisfaction were determined. Statistical analyses were performed in Excel. RESULTS: In total, 195 paediatric patients were included. Pharmacists identified 65 interventions, 95% of which were accepted. The most frequent DRPs included inappropriate drug administration (32.3%), herb-drug interactions (24.6%) and dose selection (17%). Parents' knowledge increased by 28% from baseline after pharmacist's medication counselling. Parents' drug-related needs concerning administration and side effects decreased by 67% and 49%, respectively, following the pharmacist's medication counselling. Most (75%) of the patients were able to get their treatment immediately after discharge. CONCLUSION: Clinical pharmacists can improve medication safety for children during the discharge process or consultations, by reducing prescription errors, optimising administration, counselling patients or parents and helping to ensure care continuity.

Epidemiology and economic burden of "serious" adverse drug reactions: Real-world evidence research based on pharmacovigilance data.

AIM OF THE STUDY: Serious adverse drug reactions account for 3.6% of French hospital admissions. Of these, 48.5% are, at least potentially, preventable. The first aim of post-marketing pharmacovigilance is to detect adverse drug reactions as a safety signal to improve patients' safety. Thus, this study describes the epidemiology of "serious" adverse drug reactions reported between 2015 and 2018 to a regional pharmacovigilance centre and assesses their economic burden. METHODS: All "serious" adverse drug reactions reported to a regional pharmacovigilance centre during the four-year study period were collected and cost associated. Only congenital anomalies related to "serious" adverse drug reactions were excluded. RESULTS: All 2585 "serious" adverse drug reactions reported are related to 1242 "serious" individual case safety reports. Among 58.1% of them, patients required hospital admission or a visit to the emergency room with a median cost estimated to €3725 per "serious" individual case safety report. The most "serious" adverse drug reactions reported involved gastrointestinal disorders. Fifteen percent of the imputed drugs had a narrow therapeutic index and the most frequently drug was fluindione. Finally, high relationships with an economic burden were observed for ages over or equal to 65, and imputed drugs from "Blood and Blood-Forming Organs" and "Anti-infectives for systemic use" therapeutic groups. CONCLUSION: This study provides news data on epidemiology and cost of "serious" adverse drug reactions completing the existing literature. On a regional scale, pharmacovigilance real world data could be interesting for pharmacist clinicians in common practice to improve the good use of drugs.

ATMP Environmental Exposure Assessment in European Healthcare Settings: A Systematic Review of the Literature.

Since 2007, a new class of biologic products for human use called "advanced therapy medicinal products (ATMP)" have been legally integrated in the European Medical Agency. They consist of recombinant nucleic acid, engineered cells, cells, or tissues. In the United States, ATMP fall under the regulatory framework of biological products and the term "cell and gene therapy product" is used in the legislative and regulatory documents. Potential clinical applications are broad, particularly, in the field of cancer, inherited genetic disease, and regenerative medicine. Indeed, the benefit conferred by CD19 chimeric antigen receptor T cells led to the first engineered cell therapy products to be approved by the Food and Drug Administration (FDA) in 2017. Gene therapy products to treat orphan diseases are also extensively developed with many clinical trials ongoing in the world. Nevertheless, the use of these therapeutic products is complex and requires careful considerations in the terms of regulatory and hospital setting requirements, such as storage, handling, administration, and disposal which justify the implementation of a secured medication circuit. Through this systematic review of the literature, the authors wanted to compile data on the assessment of environmental exposure related to the use of ATMP in healthcare setting to secure their medication circuit. A literature search was conducted on PubMed and Web of Science, and 32 publications dealing with environmental exposure assessment and ATMP were selected. In addition, marketed ATMPs were identified and data regarding the environmental concerns were extracted from product information sections from European Public Assessment Reports (EPAR). The environmental contamination assessments were mainly addressed in the reviews rather than in original articles related to the use of ATMP. Most of the product information sections from EPAR suggested precautions rather than requirements when dealing with environmental consideration following ATMP handling. Nevertheless, these precautions usually remain elusive especially concerning waste disposal and the detection of biological material on the work surfaces, and mainly relate to the genetically modified organisms (GMO) over non-GMO cellular products. Pharmaceutical oversight and adherence to the good preparation practices and good clinical practices are essential to ensure the safe use in term of environmental concern of these new therapeutic products in healthcare setting.

Cost-effectiveness Analysis of Innovative Therapy for Patients with Newly Diagnosed Hormone-Sensitive Metastatic Prostate Cancer.

BACKGROUND: The optimal therapeutic strategies for patients with metastatic hormone-sensitive prostate cancer (mHSPC) followed by metastatic castrate-resistant prostate cancer (mCRPC), in terms of cost and effectiveness, remains unknown. This study aims to compare the cost-effectiveness of various potential strategies, from the start of first-line treatment in mHSPC to the death of the patients. METHODS: Two Markov decision-analysis models were developed, one for cohort A "asymptomatic/mildly symptomatic patients in mCRPC", and one for cohort B "symptomatic patients in mCRPC". Each strategy reflects daily practice for mHSPC until progression in mCRPC from the start of first treatment regimen with either docetaxel or abiraterone acetate plus prednisone (AA) in mHSPC to the death of the patient. The cost-effectiveness analysis was performed from the French public health care system perspective. Only direct medical costs were included. Survival data were extracted from results of published randomized clinical trials. RESULTS: For cohort A, docetaxel followed by AA is the most cost-effective therapeutic strategy (€96,925 for 4.24 life-years). For cohort B, docetaxel followed by docetaxel is the most cost-effective therapeutic strategy (€81,463 for 4.05 life-years). Sensitivity analyses confirmed the robustness of our results except for a price reduction of 70% for AA or enzalutamide. CONCLUSION: Our approach is innovative to the extent that our analysis considers various potential strategies for metastatic prostate cancer (mPC). Our economic evaluation suggests that a price reduction of AA or enzalutamide impacts on the results. This approach must continue, including new drugs for patients with mPC.

Oral therapy adherence and satisfaction in patients with multiple myeloma.

The transition to oral therapies in patients with multiple myeloma (MM) offers potential benefits to patients; however, they must self-manage their medication and adherence plays an important role in patient care. It has been shown that patient satisfaction with their medication has a strong positive correlation with adherence in chronic diseases. The aim of this study was to estimate adherence rate of oral antimyeloma therapies and to identify risk factors for medication non-adherence. This observational, prospective, and multicentre survey based on a self-report questionnaire enrolled MM patients with at least 3 months of oral therapy. The 6-item Girerd scale and the medication possession ratio (MPR) were used for measuring medication adherence and the SATMED-Q® questionnaire was used for measuring satisfaction. An analysis of risk factors for non-adherence to oral therapy was performed using univariate analysis. A total of 101 patients participated in the survey, yielding a response rate of 87%. The prevalence of adherence to oral antimyeloma therapy was estimated at 51.5% using the Girerd questionnaire. According to the MPR, adherence was evaluated at 96% (i.e. MPR ≥ 0.80). Both methods combined, adherence was estimated at 50.5%. One risk factor for medication non-adherence was identified: Eastern Cooperative Oncology Group Performance Status > 2 (p = 0.007). One predictive factor for high medication adherence was identified: high satisfaction with treatment (p = 0.01). Identifying patients at higher risk for non-adherence allows clinical pharmacists to personalise therapeutic information and education and to improve the quality of healthcare overall.

BPDCN: When polychemotherapy does not compromise allogeneic CD123 CAR-T cell cytotoxicity.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with poor prognosis and no treatment consensus. Combining chemotherapy and immunotherapy is a promising strategy to enhance therapeutic effect. Before combining these therapies, the influence of one on the other has to be explored. We set up a model to test the combination of polychemotherapy - named methotrexate, idarubicine, dexamethasone, and L-asparaginase (MIDA) - and CD123 CAR-T cell therapy. We showed that CD123 CAR-T cells exert the same effect on BPDCN models alone, or after MIDA regimen. These data support a preclinical rationale to use immunotherapy after a treatment with polychemotherapy for BPDCN patients.

COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity.

Adaptive Immune responses generated by SARS-CoV-2 virus in convalescent patients according to disease severity remain poorly characterized. To this end, we designed a prospective study (NCT04365322) that included 60 COVID-19 convalescent patients (1-month post infection) in two cohorts respectively entitled mild illness and severe pneumonia. The monitoring of peripheral immune responses was performed using IFNᵧ ELISpot assay. The serology index of each patient was investigated at the same time. Patients with severe pneumonia were older and had more comorbidities than patients with mild illness. T-cell responses in term of frequency and intensity were clearly distinct between mild illness and severe pneumonia patients. Furthermore, our results demonstrated that recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses (Cytomegalovirus, Epstein-Barr-virus and Flu-virus). The presence of potent adaptive immunity even in patients who underwent severe pneumonia sustain the rationale for the development of protective therapeutics against SARS-CoV-2.

Investigation of the prognostic value of CD4 T cell subsets expanded from tumor-infiltrating lymphocytes of colorectal cancer liver metastases.

BACKGROUND: The positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells. METHODS: Liver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients' clinical outcomes. RESULTS: We successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3low cultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007). CONCLUSIONS: Our data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients' survival, suggesting a particular role of this T cell subset in CRC immune contexture. TRIAL REGISTRATION NUMBER: NCT02817178.

Economic evaluations of cancer immunotherapy: a systematic review and quality evaluation.

OBJECTIVES: Scientific advances in the last decade have highlighted the use of immunotherapy, especially immune checkpoint inhibitors, to be an effective strategy in cancer therapy. However, these immunotherapeutic agents are expensive, and their use must take into account economic criteria. Thus, the objective of the present study was to systematically identify and review published EE related to the use of ipilimumab, nivolumab or pembrolizumab in melanoma, lung cancer, head and neck cancer or renal cell carcinoma, and to assess their quality. METHODS: The systematic literature research was conducted on Medline via PubMed and the Cochrane Central Register of Controlled Trials to identify economic evaluations published before July 2018. The quality of each selected economic evaluation was assessed by two independent reviewers using the Drummond checklist. RESULTS: Our systematic review was based on 32 economic evaluations using different methodological approaches, different perspectives and different time horizons. Three-quarters of the economic evaluations are full (n = 24) with a Drummond score ≥ 7, synonymous of "high quality". Among them, 66% reported a strategy that was cost-effective. The most assessed immunotherapeutic agent was nivolumab. In patients with renal cell carcinoma or head and neck cancer, it was less likely to be cost-effective than in patients with melanoma or lung cancer. CONCLUSIONS: Whether or not these findings will be confirmed remains to be seen when market approval to cover more indications is extended and new effective immunotherapeutic agents become available.

Cost and efficacy of peripheral stem cell mobilization strategies in multiple myeloma.

Mobilization of peripheral blood stem cells (PBSC) can be performed using plerixafor, which is expensive, or high-dose cyclophosphamide (HDCy). We hypothesized that the overall cost of mobilization with plerixafor might not be greater if the cost of complication management was considered. We performed a cost analysis of these two strategies. This multicentric observational study recruited patients with myeloma who underwent a first PBSC mobilization. We considered direct medical costs, including hospitalization, mobilization agents, apheresis, and supportive treatments. We included 111 patients, 54 and 57 in the HDCy and plerixafor groups, respectively. Cost of mobilization with HDCy was 5097 ± 2982€ vs. 10958 ± 1789€ for plerixafor (p < 0.0001). Cost of agents used was 1287 ± 779€ vs. 6552 ± 509€, respectively (p = 0.0009). The mean number of days of hospitalization was 2 and 2.1 days, respectively (p = 0.035). All patients achieved the minimum PBSC collection target (p = 1.0); however, ASCT was performed with HDCy in 67% patients and with plerixafor in 86% (p = 0.02). Plerixafor mobilization incurred a greater cost, mostly due to the greater cost of the drug. Hospitalization length in the two groups was similar in our series. Interestingly, plerixafor appeared to be a very effective and safe mobilizing approach translating into a greater ASCT success.

A systematic review of economic evaluation in fecal microbiota transplantation.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results. OBJECTIVES: To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases. DATA SOURCES: The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019. STUDY ELIGIBILITY CRITERIA: Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster. METHODS: A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist. RESULTS: Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole. CONCLUSIONS: Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.

[Adjuvant hormonal therapy for early breast cancer: Assessment of patients' satisfaction]. / Évaluation de la satisfaction de patientes atteintes d'un cancer du sein précoce traitées en adjuvant par hormonothérapie.

INTRODUCTION: Since the cancer plan, evaluation of professional practices is essential to ensure the implementation of high-quality health care. Assess patient satisfaction is one of the pillars of high-quality health care. The main objective of the study was to assess the satisfaction of patients with early breast cancer taking a hormonal therapy, the secondary objective was to identify factors associated with their satisfaction. METHODS: The modified EORTC OUT-PATSAT-35 questionnaire was sent to a sample of patients in Franche-Comté in order to evaluate nine dimensions of satisfaction among which interpersonal skills, provided information, and overall satisfaction. For each dimension, a satisfaction score between 0 (no satisfaction) and 100 (highest satisfaction) was measured. Logistic regression analyses were used to study the factors associated with satisfaction. RESULTS: The mean overall satisfaction score for the 280 patients who answered was 73 [0-100]. Practicing an extra-professional activity was associated with higher satisfaction for several dimensions (odds ratio between 2.80 and 4.12, P<0.05) whereas it was decreased in the case of a modified appetite (odds ratio between 0.27 and 0.52, P<0.05). No link has been shown between satisfaction and adherence. DISCUSSION: The patients were satisfied and several factors impacting their satisfaction were identified, based on a questionnaire that must evolve to take into account the ambulatory aspect of their care. During the consultations, particular attention will be paid to these factors.

Interaction between phytotherapy and oral anticancer agents: prospective study and literature review.

Cancer is becoming more prevalent in elderly patient. Due to polypharmacy, older adults with cancer are predisposed to drug-drug interactions. There is also an increasing interest in the use of complementary and alternative medicine (CAM). Thirty to seventy percent of patients with cancer have used CAM. Through pharmaceutical counseling sessions, we can provide advices on herb-drug interactions (HDI). All the patients seen in pharmaceutical counseling sessions were prospectively included. Information was collected during these sessions: prescribed medication (oral anticancer agents (OAA) and other drugs), CAM (phytotherapy especially), and use of over-the-counter (OTC) drugs. If pharmacist considered an interaction or an intervention clinically relevant, the oncologist was notified. Then, a literature review was realized to identify the potential HDI (no interactions, precautions for use, contraindication). Among 201 pharmacist counseling sessions, it resulted in 104 interventions related to 46 HDI, 28 drug-drug interactions and 30 others (wrong dosage, omission…). To determine HDI, we review 73 medicinal plants which are used by our patients with cancer and 31 OAA. A total of 1829 recommendations were formulated about 59 (75%) medical plants and their interaction with an OAA. Herb-drug interactions should not be ignored by healthcare providers in their management of cancer patients in daily practice.

Economic Burden of Metastatic Clear-Cell Renal Cell Carcinoma for French Patients Treated With Targeted Therapies.

BACKGROUND: Targeted therapies have transformed the treatment of metastatic clear-cell renal cell carcinoma (mccRCC). Despite the importance of mccRCC, studies on its economic burden in daily practice are sparse. The purpose of this retrospective study was to evaluate cost of illness for 224 patients with mccRCC included in the cohort published by Thiery-Vuillemin et al (Factors influencing overall survival for patients with metastatic clear-cell renal cell-carcinoma in daily practice. Clin Genitourin Cancer 2018; 16:e297-305), and then to determine the explanatory factors of cost of illness. PATIENTS AND METHODS: The study was performed from the French Public Healthcare System perspective with lifetime horizon. Only direct medical costs were included. Multiple linear regression was used to search for explanatory factors of cost of illness. The robustness of results was assessed. RESULTS: The mean cost of illness was estimated at €71,185 ± 52,683. Outpatient/inpatient treatment and hospitalization represented 76.0% and 19.7% of this cost, respectively. After adjustment, 5 explanatory factors were identified: time of disease control for the metastatic first-line treatment ≥6 months, number of lines of treatment >2, nephrectomy at metastatic stage, lack of metastases at presentation, and age at metastatic diagnosis younger than 65 years. Individually, they increased cost of illness by 128%, 95%, 53%, 53%, and 23%, respectively. CONCLUSION: Although it is difficult to transpose our economic evaluation results to those obtained in other countries, it should be noted that our findings were consistent with them and robust. To our knowledge, our study was the first to accurately identify explanatory factors of cost of illness. Identifying them could enable us to predict the budgetary effect on a regional level of managing patients who began their first-line treatment with a targeted therapy.

[Acceptability and effectiveness of immunotherapy in patients with melanoma]. / Acceptabilité et efficacité des immunothérapies dans le traitement du mélanome.

The immunotherapies known as "inhibitors of checkpoint" (ICP) are monoclonal antibodies used since 2010 and have dramatically modified the management of the advanced or metastatic melanomas. By reactivating the anti-tumoral immune response, these antibodies can activate the immune system in all the tissues with a risk to induce immune related adverse events (IrAE). Thus, the adverse effect's profile of ICP is considered as very different from that usually associated with conventional chemotherapies. The objectives of our retrospective monocentric study were the evaluation of the real life's safety and efficiency of the ipilimumab and the pembrolizumab in patients with an advanced melanoma. Seventy-two patients treated by ipilimumab and\or pembrolizumab between August 1st, 2008 and December 31st, 2016 were investigated. The main IrAE occurring involved the gastro- intestinal, skin, and the endocrine systems. The average onset time of IrAE was 39, 104 and 68 days, respectively and their respective duration was of 67, 50 and 111 days. There were 13 events of grade III and IV along with one death. The overall survival was 5 months for the patients treated in monotherapy with ipilimumab, and 14 months for those treated by pembrolizumab. Our real life's study tends to confirm the current safety profile of ICP treatment. Moreover and according to our analyses, the drug sequence seems to have a global survival impact.