Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma.

This phase I dose-escalation/expansion study evaluated isatuximab (anti-CD38 monoclonal antibody) monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Patients progressing on or after standard therapy received intravenous isatuximab (weekly [QW] or every 2 weeks [Q2W]). The primary objective was to determine the maximum tolerated dose (MTD) of isatuximab. Overall, 84 patients received ≥ 1 dose of isatuximab. The MTD was not reached; no cumulative adverse reactions were noted. The most frequent adverse events were infusion reactions (IRs), occurring in 37/73 patients (51%) following introduction of mandatory prophylaxis. IRs were mostly grade 1/2, occurred predominantly during Cycle 1, and led to treatment discontinuation in two patients. CD38 receptor occupancy reached a plateau of 80% with isatuximab 20 mg/kg (highest dose tested) and was associated with clinical response. In patients receiving isatuximab ≥ 10 mg/kg, overall response rate (ORR) was 23.8% (15/63), including one complete response. In high-risk patients treated with isatuximab 10 mg/kg (QW or Q2W), ORR was 16.7% (3/18). Median (range) duration of response at doses ≥ 10 mg/kg was 25 (8-30) weeks among high-risk patients versus 36 (6-85) weeks for other patients. In conclusion, isatuximab demonstrated a manageable safety profile and clinical activity in patients with RRMM.

Drowsiness and uncommon fever in a child after cannabis ingestion.

Trivialization of cannabis consumption goes hand in hand with a growing exposure of children and the number of cannabis poisoning cases is steadily increasing. As clinical presentation can be different from what is currently seen in adults, added to the fact that it is not always suspected, diagnosis of cannabis intoxication in children is often delayed or missed. A 16-month-old girl was admitted to the pediatric emergency unit for an important drowsiness combined to moderate fever. After elimination of infectious causes, a toxic origin was considered and biological analyses led to the diagnosis of involuntary acute cannabis intoxication. In conclusion, cannabis intoxication in child has uncommon presentations compared to that seen in adults. In this context, biological analyses have a great importance for a rapid diagnosis and also for the understanding intoxication circumstance. This is of paramount importance because it may lead to consider child protection measures.

Therapeutic drug monitoring of mitotane: Analytical assay and patient follow-up.

Adrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal gland. Mitotane (o,p'-DDD) is the most effective chemotherapy for ACC. According to the literature, mitotane plasma trough concentrations within 14-20 mg L-1 are correlated with a higher response rate with acceptable toxicity. Therapeutic drug monitoring (TDM) of mitotane is therefore recommended. The aim of this study was to propose a robust and simple method for mitotane quantification in plasma. The validation procedures were based on international guidelines. Sample preparation consisted of a single protein precipitation with methanol using 100 µL of plasma. The supernatant was submitted to liquid chromatography coupled with ultra-violet detection at 230 nm. Mitotane retention time was 7.1 min. The limit of detection was 0.1 mg L-1 and the limit of quantification was 0.78 mg L-1 . The assay demonstrated a linear range of 0.78-25 mg L-1 with correlation coefficients (r2 ) at 0.999. Inter- and intra-assay precision was <4.85%. Evaluation of accuracy showed a deviation <13.69% from target concentration at each quality control level. This method proved easy and rapid to perform mitotane TDM and required a small volume of sample. It was successfully applied to routine TDM in our laboratory.

A Slight Smell of Lemon.

We present here an example of urine substituted with a yellow cleaning product that leads us to develop the main risks to consider in urine toxicology analysis, ie, adulteration and analytical interferences, and how to deal with them. This grand round highlights the importance of the dialog between the clinician and a TDM consultant for optimal care of the patient.

False negative on a proven involuntary intoxication in two children with lorazepam.

Children aged between 1 to 4 years are the most at risk of unintentional poisonings. Benzodiazepines are the most medicine often cause of the poisoning. Among the twenty-two most prescribed benzodiazepines in France, lorazepam ranks fifth behind zolpidem, alprazolam, bromazepam and zopiclone. However the automated assay currently available does not allow to detect and/or to quantify lorazepam. The alternative to the immunoassay is the liquid chromatography coupled with mass spectrometry (HPLC/MS). This technique, highly sensitive and specific, requires a pre-treatment phase and a good technical proficiency, justifying specialized staff. The clinical cases presented here illustrate the major interest of availability to this type of technology in routine and 24h/24h.

Validation of a fast UPLC-MS/MS method for quantitative analysis of opioids, cocaine, amphetamines (and their derivatives) in human whole blood.

BACKGROUND: Conventional methods for analysis of drugs of abuse require multiple assays which can be both expensive and time-consuming. This work describes a novel, rapid, simple and sensitive method for the quantification of 14 illicit drugs and their metabolites in whole blood. Results/methodology: This method employed a rapid liquid-liquid sample extraction of whole blood followed by UPLC-MS/MS analysis. Calibration curves were validated for analysis of appropriate concentrations. Inter- and intra-assay variations were <14.8%. Deviation of accuracy was <14.9% from target concentration for each quality control level. CONCLUSION: This work described the development and the full validation of a precise, sensitive and accurate assay. After validation, this new assay was successfully applied to routine toxicological analysis.