Single-agent daratumumab in very advanced relapsed and refractory multiple myeloma patients: a real-life single-center retrospective study.

The anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID), or who are double refractory to a PI and an IMID. To date, no real-life data on the efficacy and tolerance of daratumumab in this setting are available. We report here the results of a single-center series of 41 RRMM patients treated with single-agent daratumumab outside clinical trials. Patients received a median number of 4 prior therapies. All patients were previously exposed to PI and IMID and all patients were refractory to the last line of therapy. Most patients presented with high-risk characteristics, including 24% adverse cytogenetics (del17p/t(4,14)), 31% extramedullary disease and 12% circulating plasmacytosis at time of daratumumab therapy. The overall response rate was 24%, including 5% very good partial response or better. After a median follow-up of 6.5 months, all patients experienced disease relapse. The median progression-free survival was 1.9 months. At the time of disease progression, 44% of patients did not receive subsequent therapy. The median overall survival was 6.5 months. No new safety signal was identified. These real-life results revealed modest efficacy of single-agent daratumumab in advanced patients with RRMM in comparison with data from clinical trials.

Analysis of cost-effectiveness of chemotherapeutic agents and new therapies for the management of unresectable and metastatic melanoma.

BACKGROUND: The advent of targeted therapies and immunotherapies has revolutionized metastatic melanoma (MM) management but their use is associated with high daily costs compared to chemotherapies: €2 for dacarbazine versus €175 for immunotherapies and €413 for targeted therapies. While overall survival (OS) has increased, healthcare expenditures are expected to double by 2030. OBJECTIVES: The aim of this study was to estimate the median OS and costs for MM patients in order to evaluate the effectiveness of new biological or targeted therapies (NT) used since 2013 compared to chemotherapies. MATERIALS & METHODS: This was a retrospective monocentric cost-effectiveness analysis performed in CHU Nantes (Nantes University Hospital). All MM patients treated with conventional chemotherapy as first-line treatment between 2008 and 2012 were included (CHEMO group). The same number of patients treated with NT as first-line between 2013 and 2017 were included (NT group). RESULTS: In total, 161 patients were included in each group. The mean age at diagnosis was 64.7±2.4 years in the CHEMO group and 65.3±2.4 years in the NT group (not significant). The men/women ratio was 1.48 and 1.27, respectively, (not significant). The median OS was 158 days in the CHEMO group and 395 days in the NT group (p<0.001). Treatment cost was €10,280/patient versus €94,676/patient, respectively. The mean incremental cost-effectiveness ratio was €90,184/LY (95% CI: €59,637; €166,395). CONCLUSION: Our study assessed clinical and economic features associated with MM management before and after the advent of NT. Costs and life expectancy have increased. NT appears to be cost-effective.

Production and stability study of a hospital parenteral nutrition solution for neonates.

Standard parenteral nutrition solutions are mixtures comprising interacting components that may degrade themselves over time. The objective of this study was to investigate the physicochemical and microbiological stability of a hospital preparation for parenteral nutrition in neonatology. The analyses were performed throughout the storage of the preparations at 2-8 °C (up to 4 months). The extent of stability was based on the determination of amino acids dosage, visual and physicochemical properties (glucose and electrolytes concentrations, pH and osmolality measurements, particle counting) and microbiological analysis (sterility test). A thermal degradation of ascorbic acid was conducted to evaluate the antioxidant properties of the parenteral mixture. Physicochemical and microbiological controls were found to comply with the specifications. Amino acids showed a good stability throughout the 4months storage except for cysteine, which was progressively degraded to cystine, conferring a yellow coloration to parenteral solutions. Parenteral nutrition standards solutions remain stable for 4 months at 2-8 °C, ensuring safe administration in preterm infants.

Real-life patterns of use and effectiveness of bortezomib: the VESUVE cohort study.

In response to a regulatory request for real-life data on patterns of use and survival outcomes, 793 patients initiating bortezomib for multiple myeloma in France (May 2004-April 2006) were included in this observational study. Data were collected from medical files and patients were followed for 2 years, with vital status collected after 3 years. In total 779 patients were analyzed: 83.1% had immunoglobulin G (IgG) or IgA M-component, mean age was 65.7 years and 46.5% were female. Bortezomib was initiated as third-or-later line in 82.0%. For 75.9%, the starting dose was 1.3 mg/m(2); 42.6% had bortezomib alone, 54.0% with dexamethasone. The mean number of bortezomib cycles was 5.0. Three-year overall survival from bortezomib initiation was 31.4% (95% confidence interval, CI [28.1; 34.7]) and median overall survival was 19.6 months. Two-year progression-free survival was 12.0% (95% CI [9.8; 14.4]), and median progression-free survival was 7.2 months. Overall best response was 44.0%. Survival outcomes during real-life use of bortezomib were within the range of those reported in clinical trials.

Good practice in antibiotic use: what about linezolid in a French university hospital?

OBJECTIVE: Linezolid represents an important advance in the treatment of methicillinresistant staphylococci. Its effectiveness should be preserved by appropriate uses. The aims of this survey were to describe the use of linezolid in clinical practice and to assess its overall safety. METHODS: This retrospective observational study included patients treated with linezolid in 2008 in all departments at the CHU Nantes. A data-collection card was completed using the patients' medical files. RESULTS: A total of 179 patients from 23 different departments were included. Fifty-four per cent of indications were outside the Marketing Authorization criteria, and were mainly osteoarticular infections and septicaemia (22% and 8% of total prescriptions, respectively). Inefficacy of first-line antibiotic treatment (23%) and alterations in renal function (23%) were the main reasons for using linezolid, which was prescribed as a first-line therapy in 28% of patients. Fifty-three per cent of infections were documented microbiologically, of which 58% were due to a methicillin-resistant Staphylococcus. CONCLUSIONS: Linezolid seems to be a possible therapeutic strategy in case of multiresistant bacteria and/or complex clinical situations. Because many prescriptions fall outside the Marketing Authorization criteria, this study highlights the need to have clinical data available for such situations.

Comparative toxicity and efficacy of combined radioimmunotherapy and antiangiogenic therapy in carcinoembryonic antigen-expressing medullary thyroid cancer xenograft.

UNLABELLED: A significant antitumor effect was previously observed with radioimmunotherapy using anti-carcinoembryonic antigen (131)I-F6 monoclonal antibody in medullary thyroid cancer-bearing nude mice. Nevertheless, no complete response was observed. As seen with chemotherapy, drugs targeting the tumor microenvironment might improve radioimmunotherapy efficacy. This study evaluated the toxicity and efficacy of combining radioimmunotherapy with thalidomide or a cyclopeptidic vascular endothelial growth inhibitor (CBOP11) in mice grafted with the TT human medullary thyroid cancer cell line. METHODS: Six to 10 nude mice treated with 92.5 MBq of (131)I-F6 in association with 200 mg/kg/d of oral thalidomide during 20 d by force-feeding or 0.45 mg/kg/d of CBOP11 during 25 d using subcutaneous minipumps were compared with control mice receiving either treatment or naked F6 or nonspecific (131)I-734. Combined therapies included (131)I-F6 at day 0 followed by thalidomide between days 20 and 40, thalidomide between days 0 and 20 followed by (131)I-F6 at day 25, (131)I-F6 at day 0 and CBOP11 between days 0 and 25, CBOP11 between days 0 and 25 followed by (131)I-F6 at day 25, and (131)I-F6 at day 0 followed by CBOP11 between days 20 and 45. Animal weight, hematologic toxicity, tumor volume, and serum calcitonin were monitored for the following 3 mo. Improvement of (125)I-F6 tumor biodistribution by antiangiogenic drug was studied after pretreatment by thalidomide. Follow-up of the tumor after combined antiangiogenic and radioimmunotherapy therapies was performed by histology studies. RESULTS: Combined associations, as compared with radioimmunotherapy alone, increased leukopenia but not thrombocytopenia. Tumor volume-quadrupling time (TVQT) was 22.8 +/- 3.3 d in the control group, 29.9 +/- 3.6 d in the group treated with thalidomide, 34.6 +/- 4.4 d in the group treated with CBOP11, and 51.0 +/- 2.8 d after radioimmunotherapy alone. As compared with radioimmunotherapy, TVQT was significantly longer (P < 0.01) after thalidomide followed by radioimmunotherapy (69.83 +/- 3.9), CBOP11 followed by radioimmunotherapy (71.3 +/- 6.1), and CBOP11-radioimmunotherapy in concomitance (64.2 +/- 6.1). Nevertheless, TVQT was not increased after radioimmunotherapy followed by thalidomide (48.8 +/- 4) and radioimmunotherapy followed by CBOP11 (56.8 +/- 4.8). Surprisingly, pretreatment by CBOP11 or thalidomide sensitized larger tumors (>300 mm(3)) to radioimmunotherapy. Change in calcitonin levels confirmed morphologic tumor response. Tumor uptake 24 h after injection of (125)I-F6 was 4.5 +/- 0.6 percentage injected dose per gram (%ID/g) without pretreatment and 8.7 +/- 1.3 %ID/g with pretreatment by thalidomide. An increase of the antitumor effect observed using the antiangiogenic drug combined with radioimmunotherapy was correlated with a decrease of blood vessels shown by von Willebrand immunostaining. CONCLUSION: Pretreatment with antiangiogenic therapies improved radioimmunotherapy efficacy, with acceptable toxicity. Future investigations will be performed to understand how antiangiogenic agents sensitize large tumors to radioimmunotherapy.

Silent hypersensitivity to Escherichia coli asparaginase in children with acute lymphoblastic leukemia.

This prospective study aimed to assess the incidence of silent hypersensitivity to Escherichia coli asparaginase in the treatment of acute lymphoblastic leukemia (ALL). Thirty-three children with newly diagnosed ALL were included in the study and treated according to the FRALLE 2000 protocol. The 'A group' (n = 18) differed from the 'B-T group' (n = 15) by a less intensive chemotherapy, the absence of concurrent prednisone therapy, and different asparaginase administration modalities during the second intensification. Asparagine, asparaginase activity, and anti-asparaginase antibodies were measured in each phase before the next injection of asparaginase. Eighteen percent of children presented a silent hypersensitivity. Most of them were in the 'B-T group' (p = 0.07), and maintained low antibody titers throughout the treatment. Clinical hypersensitivity was statistically more frequent in group A (p = 0.002), and allergy occurred mainly during the second intensification when antibody concentrations were significantly increased. We did not find any significant difference between asparaginase activity or asparagine depletion between the silent hypersensitivity and clinical allergy groups. In all, the results of this study suggest that chemotherapy and corticosteroid therapy associated with asparaginase treatment can lower antibody production and contribute to maintaining a silent hypersensitivity state.

[Outpatient chemotherapy and oncology network : Onco Pays-de-la-Loire experiment]. / Chimiothérapie à domicile et réseau ville-hôpital : expérience du réseau Onco Pays-de-la-Loire.

Many regulatory rules related to home-based care for cancer patients issued during the recent years. More precisely, the French Plan cancer and the December 2004 << arrêté >> aim at << facilitating home-based chemotherapy by injection >> only << within the framework of a network of health in oncology >>, this in order to improve the quality of care and quality of life of patients. In this context, the Onco Pays-de-la-Loire network launched a project with centralised preparations of chemotherapy administred at home. We describe in this study the first results of this experiment. 41 patients have been treated and 224 cytotoxic drugs sended since january 2007 (56 % with trastuzumab, 19 % with gemcitabin, 13 % with methotrexate and 12 % with fluorouracil). No major problem was detected, 1,9 % of the preparations were destroyed. Satisfaction of outpatient healthcare professionals was good. A comparison of estimated costs revealed reductions in costs for outpatient chemotherapy. These first results validate the interest of cancer treatment at home for this kind of patients, and show the importance of nurse and pharmaceutical coordination.