Prognosis of hyperviscosity syndrome in newly diagnosed multiple myeloma in modern-era therapy: A real-life study

Hyperviscosity syndrome (HVS) is a rare complication of newly diagnosed multiple myeloma (NDMM) related to high tumour burden. Studies about the prognosis of HVS in modern-era therapy for NDMM are missing. We investigated a retrospective cohort study of NDMM with HVS between 2011-2021. Thirty-nine NDMM patients with HVS were included. HVS presentation was heterogeneous, with asymptomatic, mild, and neurological forms in 23%, 59%, and 18% of cases, respectively. No thrombosis or major bleeding was observed. Therapeutic plasma exchanges were used in 92% of patients, which were effective and well tolerated. No rebound effect was observed. All patients except one had at least one CRAB criterion. Most of the patients received bortezomib and high-dose steroids (95%) associated with an immunomodulatory drug (43%) or alkylating agents (42%). HVS in NDMM patients had dismal overall survival matched to multiple myeloma patient controls (without HVS) in our center (median: 3.6 vs. 7.7 years, p=0.01), as confirmed by multivariate analysis. Early deaths (in the first two months) occurred in 21% of older patients (>65 years). HVS in NDMM patients is a rare but life-threatening complication associated with high lethality in older patients and be a potential dismal prognosis factor in the modern treatment era

Phylloplane microbiome diversity in fructan- and non-fructan accumulating grassland species and its relationship with carbohydrate metabolism of the host plant

International audienc

Phylloplane microbiome diversity in fructan- and non-fructan accumulating grassland species and its relationship with carbohydrate metabolism of the host plant

International audienc

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against <it>Plasmodium falciparum</it>

Abstract Background Quinine (QN) remains the first line anti-malarial drug for the treatment of complicated malaria in Europe and Africa. The emergence of QN resistance has been documented. QN resistance is not yet a significant problem, but there is an urgent need to discover partners for use in combination with QN. The aim of the study was to assess the in vitro potentiating effects of atorvastatin (AVA), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with QN against Plasmodium falciparum and to evaluate whether the effects of AVA could be associated with gene copy number or mutations in genes involved in QN resistance, such as pfcrt, pfmdr1, pfmrp and pfnhe. Methods The susceptibilities to combination of AVA with QN were assessed against 21 parasite strains using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfcrt, pfmdr1, pfmdr2, pfmrp genes. In addition, the number of DNNND, DDNHNDNHNN repeats in pfnhe-1 ms4760 and the ms4760 profile were determined for each strains of P. falciparum. Results AVA demonstrated synergistic effects in combination with QN against 21 P. falciparum strains. The QN IC50 was reduced by 5% (0% to 15%; 95%CI: 1%-8%), 10% (3% to 23%; 95%CI: 7%-14%) and 22% (14% to 40%; 95%CI: 19%-25%) in presence of AVA at concentrations of 0.1, 0.5 and 1.0 μM, respectively. These reductions were all significant (p 50 in presence of AVA was not significantly correlated with the QN IC50 (r = 0.22, P = 0.3288) or the AVA IC50 (r = 0.03, P = 0.8946). The synergistic effect of AVA in combination with QN was not significantly associated with polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes that could be involved in QN resistance. The synergistic effect of AVA on QN responses was not significantly associated with pfmdr1 copy number (P = 0.0428). Conclusion The synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance. The different mechanisms of drug uptake and/or mode of action for AVA compared to the other anti-malarial drugs, as well as the AVA-mediated synergy of the anti-malarial effect of QN, suggests that AVA will be a good candidate for combinatorial malaria treatment. All of these observations support calls for both an in vivo evaluation with pharmacokinetic component and clinical trials of AVA as an anti-malarial therapy.</p

Prérequis pour une production académique des cellules CART conforme aux bonnes pratiques pharmaceutiques (BPF). Recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

The extraordinary and unexpected success of cellular immunotherapy using genetically engineered T-cells to express a chimeric antigen receptor (CAR) targeting CD19, in the treatment of refractory or relapsing B-hematological malignancies, has provided a real therapeutic hope. Indeed, remission rates reach more than 80 % in patients at a stage, without any other possibilities of treatment, notably in the child's acute lymphoblastic leukemia. These results, initially resulting from academic research, led to Food and Drug accreditation for market access of two innovative autologous therapy drugs, Kimryah® and Yescarta®. Based on the impressive clinical results, mainly so far in hematological malignancies (LAL, MM, LBDGC, etc.), the development of several types of cells expressing a CAR receptor suggests a wide range of future applications, particularly in the field of solid tumors. However, while the development of CAR-T cells now appears to be in the hands of private pharmaceuticals companies, the logistical constraints, the cryopreservation and the very high cost of these personalized medicines may ultimately limit their use. The development of academic productions by CAR-T cells could bypass some of these disadvantages. The strong innovation capacity of healthcare institutions associated with research units allows them to identify the ideal tumor target and efficient performing cells. Thus, authorized production platforms could allow for shorter administration times and reasonable production costs for national health systems. The aim of this workshop is to identify the requirements for the academic production of CAR-T cells, while respecting the research standards useful to establish proof of concept, but also at the preclinical development stage, leading in fine to the manufacture, through an authorized pharmaceutical establishment, of the innovative therapy drug, and in accordance with Good Manufacturing Practice (GMP). The ultimate goal is to make these innovative and high-performance medicines available to as many patients as possible

Condition de réalisation de la cytaphérèse pour la mise à disposition du matériel biologique nécessaire à la production de CAR T-cells commerciaux : avis d’experts proposé par la SFGM-TC

International audienc