French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real-world IFM study from the DESCAR-T registry.

Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

[Rituximab immunomonitoring in autoimmune diseases: a support tool in clinical practice?] / Immunomonitoring du rituximab appliqué aux maladies auto-immunes : une aide pour la pratique clinique ?

INTRODUCTION: Immune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring. METHODS: All the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included. RESULTS: Several medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies. CONCLUSION: This detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.

[Kinetic and organization of granulocytes transfusion: a case report]. / Transfusion thérapeutique de granulocytes : cinétique et aspects organisationnels autour d'un cas clinique.

BACKGROUND: Therapeutic granulocyte transfusion remains an indication for neutropenic sepsis associated with prolonged neutropenia. However, harvest complexity and lack of proved efficacy mark the limits of its development. CASE REPORT: A 58-year old man received allogeneic stem cell transplantation for osteomyelofibrosis. Six months later, after a transplant rejection, he presented with perineal cellulitis from hemorrhoid origin, without any microbiological documentation. The evolution was unfavorable despite antibiotic and antifungal therapy. A set of seven granulocytes transfusions was initiated. Re-circulation of granulocytes analysis showed an initial increase (H2) followed by a decrease (H8) reaching the basal rate at H16. No toxicity has been reported during or following the transfusions. Clinical improvement has been reported five days after the first transfusion, scaring over at D15, without any neutrophil recovery. CONCLUSION: In 2014, granulocyte transfusion therapy is indicated for severe infection associated with long-term neutropenia. Minimal circulation of transfused cells in our observation and fast clinical improvement suggest the concentration of granulocytes on the infected area.

Generation of oxidative stress in human cutaneous models following in vitro ozone exposure.

Ozone, one of the main components of photochemical smog, represents an important source of environmental oxidative stress. The skin, being the outermost barrier of the body, is directly exposed to environmental oxidant toxicants. Skin sebum and cellular plasma membrane lipids contain polyunsaturated fatty acids which are primary targets for ozone and free radical attack induced lipid peroxides. These ozonation processes in skin can also generate aldehydes, hydroxyhydroperoxides and specific Criegee's ozonides. In order to evaluate in vitro human skin susceptibility to ozone, we have exposed cultured immortalized human keratinocytes (DK7-NR) and the reconstructed human epidermis Episkin to 10 ppm of ozone in a specific incubator. We measured the formation of protein carbonyls by an ELISA method and monitored the oxidative stress using the fluorogenic probe 2',7'-dichlorofluorescin-diacetate (DCFH-DA). Results showed a time-dependent increase of fluorescence levels (linked to oxidative stress) in both models exposed to ozone. Using this protocol, we investigated the protective potential of different products including vitamin C, a thiol derivative and a plant extract. All products dramatically reduced oxidative responses during ozone exposure. Decreases observed in fluorescence levels were between 60 and 90% as compared to non-protected controls. These results demonstrate: (a) cutaneous in vitro models are remarkably susceptible to oxidative stress generated by an environmental air pollutant as ozone, and (b) raw antioxidants, thiols and vitamin C were efficient products to prevent ozone induced cellular oxidative damage.