CAR T-cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real-life results of the LOC network.

The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T-cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR-T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty-seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T-cells (tisa-cel: N = 16, axi-cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow-up after leukapheresis was 20.8 months. The best response after CAR-T cells was complete response in 16 patients (64%). One-year progression-free survival from leukapheresis was 43% with a plateau afterward. One-year relapse-free survival was 79% for patients in complete or partial response at CAR T-cell infusion. The median overall survival was 21.2 months. Twenty-three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T-cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p < 0.001). This series represents the largest cohort of PCNSL treated with CAR T-cells reported worldwide. CAR T-cells are effective in relapsed PCNSL, with a high rate of long-term remission and a reassuring tolerance profile. The results seem clearly superior to those usually observed in this setting.

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.

Layer-by-layer bioassembly of cellularized polylactic acid porous membranes for bone tissue engineering.

The conventional tissue engineering is based on seeding of macroporous scaffold on its surface ("top-down" approach). The main limitation is poor cell viability in the middle of the scaffold due to poor diffusion of oxygen and nutrients and insufficient vascularization. Layer-by-Layer (LBL) bioassembly is based on "bottom-up" approach, which considers assembly of small cellularized blocks. The aim of this work was to evaluate proliferation and differentiation of human bone marrow stromal cells (HBMSCs) and endothelial progenitor cells (EPCs) in two and three dimensions (2D, 3D) using a LBL assembly of polylactic acid (PLA) scaffolds fabricated by 3D printing. 2D experiments have shown maintain of cell viability on PLA, especially when a co-cuture system was used, as well as adequate morphology of seeded cells. Early osteoblastic and endothelial differentiations were observed and cell proliferation was increased after 7 days of culture. In 3D, cell migration was observed between layers of LBL constructs, as well as an osteoblastic differentiation. These results indicate that LBL assembly of PLA layers could be suitable for BTE, in order to promote homogenous cell distribution inside the scaffold and gene expression specific to the cells implanted in the case of co-culture system.

Cetuximab-induced aseptic meningitis: case report and review of a rare adverse event.

BACKGROUND: Cetuximab is a commonly used antibody agent in the treatment of colorectal or head and neck cancer. Although it is generally well tolerated in most patients, cetuximab has been associated with some rare but serious adverse events. Aseptic meningitis is one such distinctly uncommon adverse drug reaction. CASE PRESENTATION: We present the case of a middle-aged Caucasian patient, who presented with fever and headache within a few hours of starting cetuximab therapy and was diagnosed with cetuximab-induced aseptic meningitis after a complete workup. CONCLUSION: To our knowledge, this is the ninth case of cetuximab-induced aseptic meningitis reported in literature. Because of a nonspecific clinical presentation, this adverse drug reaction can be easily misdiagnosed. It is important to increase awareness of this potentially severe reaction among oncologists.

Liquid chromatography with tandem mass spectrometry for the simultaneous identification and quantification of cardiovascular drugs applied to the detection of substandard and falsified drugs.

The counterfeiting of pharmaceuticals has been detected since about 1990 and has alarmingly continued to pick up steam. We have been recently involved in an evaluation program of some of the most commonly prescribed cardiovascular drugs in Africa, for analysing an important number of tablets or capsules obtained from different places in seven African countries. A reversed-phase high-performance liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously control the identity and the quantity of acenocoumarol, amlodipine, atenolol, captopril, furosemide, hydrochlorothiazide and simvastatin in tablets. Their separation was performed on a Kinetex® C(18) (100 mm × 2.1 mm inside diameter, 2.6 µm) column using a gradient elution of 20 mM ammonium formate buffer and acetonitrile (90:10 10:90 v/v) at a flow rate of 0.5 mL/min. The analytes were detected using electrospray ionisation tandem mass spectrometry in both positive and negative modes with multiple reaction monitoring. Tandem mass spectrometry fragmentation patterns of captopril, furosemide and acenocoumarol, up to now not detailed in the literature, were also studied to assist in the selection of the most relevant transitions towards the objectives. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, trueness, precision, limits of detection and quantification. It has been successfully applied to the control of oral forms of seven cardiovascular drugs collected in African countries.