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Chimeric antigen receptor T cells (CAR T cells) can induce prolonged remission in a substantial subset of patients with relapse/refractory lymphoma. However, little is known about patients' life after CAR T-cell therapy. We prospectively assessed the multidimensional recovery of lymphoma patients in remission, before leukapheresis, before CAR T-cell infusion, and 3, 6, and 12 months thereafter. Validated tools were used to measure lymphoma-related and global health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy-Lymphoma [FACT-Lym] and EQ-5D-5L), cognitive complaint (FACT-Cognition), fatigue (FACIT-Fatigue subscale), psychological status (Hospital Anxiety and Depression Scale, Post-Traumatic Check List Scale), and sexuality (Relationship and Sexuality Scale). Beyond 12 months of remission, we also surveyed physical, professional, sexual, and general life status. At 3, 6, and 12 months, 53, 35, and 23 patients were evaluable, respectively. Improvement in lymphoma-related HRQoL was clinically relevant at 3, 6, and 12 months with a mean change from baseline of 10.9 (95% confidence interval [CI]: 5.8; 16.1), 12.2 (95% CI: 4.2; 20.1), and 11.72 (95% CI: 2.06; 21.38), respectively. Improvement in global HRQoL, fatigue, and anxiety was clinically relevant, but 20%-40% of patients experienced persistent fatigue, psychological distress, and cognitive complaints over time. Beyond 12 months after CAR T cells, 81.8% of 22 evaluable patients were satisfied with their daily life. Physical activity, professional, sexual, and global well-being had returned to prediagnosis levels in nearly half of the patients. We found an improvement in HRQoL after CAR T-cell therapy including anxiety, depression, sexual satisfaction, and general well-being. However, not all patients recover a "normal life." Further research is needed to determine which patients are at risk of quality-of-life impairment to improve recovery after CAR T-cell infusion., Competing Interests: The authors report the following competing interests: Aline Moignet: Honoraria from Kite/Gilead. Fanny Colin: Honoraria from Kite/Gilead. Roch Houot: Honoraria from Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda and Roche; and consultancy at Kite/Gilead, Novartis, Bristol‐Myers Squibb/Celgene, ADC Therapeutics, Incyte, Miltenyi. Amélie Anota: Consultancy for Amgen, Ipsen, AstraZeneca, Kite/Gilead. Guillaume Manson: Honoraria from Chugai, Kite/Gilead, Takeda. Loïc Ysebaert: Consultancy at Beigene, Bristol‐Myers Squibb/Celgene, Janssen, Kite/Gilead, and Roche, and is on the speaker's bureau of AstraZeneca. Sophie De Guibert: Honoraria from Kite/Gilead and Novartis., (© 2024 The Authors. HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Ibrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL). Absolute lymphocyte count (ALC) is a clinical criterion used for the monitoring of CLL. Ibrutinib has several effects on lymphocytes, and has highly variable pharmacokinetics (PK). The objective of this work was to build a PK-pharmacodynamic (PD) model describing ALC dynamics under ibrutinib treatment in patients with CLL. ALC observations before and after ibrutinib treatment initiation in patients with CLL were included in the analysis. A population PK-PD model was developed based on physio-pharmacological knowledge. Individual PK concentrations at each hospital visit were included in the model. The association between PD parameters and lymphocytosis, and between PD parameters and response to treatment were assessed. A total of 94 patients, 658 ALC and 1,501 PK observations were included in model development. The final PK-PD model accurately described ALC dynamics for different patient profiles. It consisted in two compartments (tissues and blood circulation) with ibrutinib plasmatic concentration inducing two drug effects: stimulation of lymphocyte redistribution and death. Patients with hyperlymphocytosis had significantly higher tissues to circulation baseline lymphocyte count ratio, and lower death effect. Patients who progressed under ibrutinib had significantly lower baseline lymphocyte counts in tissues (2-fold lower) and blood (3-fold lower). The first PK-PD model for ALC in patients with CLL under ibrutinib treatment was developed. This model suggests that estimated lymphocyte counts in tissues and blood could be used as an early predictor of response in patients with CLL., (© 2021 The Authors Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

This study evaluated the serum concentrations of lipids, lipoproteins, apolipoproteins, and high-density lipoprotein (HDL) subfractions in Brazilian adults. We analyzed the distribution of lipids in HDL2 and HDL3 in a normolipidemic population without evidence of established cardiovascular disease (CVD). A total of 93 males and 92 females, healthy and normolipidemic, volunteered to be submitted to a clinical examination, a blood collection, and to answer a questionnaire aimed at determining signs and symptoms of atherosclerotic disease. Their fasting plasma lipid, lipoproteins, apolipoproteins, and the cholesterol and triglyceride concentrations in HDL2 and HDL3, isolated by microultracentrifugation, were determined by enzymatic-colorimetric methods. The interpercentile intervals (2.5-97.5) for the population were established as being 5-18 mg/dL in men and 4-28 mg/dL in women for HDL2 cholesterol (HDL2chol) and 1-57 mg/dL in men and 2-61 mg/dL in women for HDL3 cholesterol (HDL3chol). HDL2 triglyceride levels (HDL2Tg) in men were 1-26 mg/dL and in women 2-28 mg/dL; moreover, the HDL3 triglyceride (HDL3Tg) intervals were established as 4-46 mg/dL for both sexes. The determination of reference ranges for lipids in HDL subfractions in populations without clinical atherosclerosis, is an useful tool for metabolic, diagnostic, and therapeutic approaches. We determined the intervals for HDL2chol, HDL3chol, HDL2Tg, and HDL3Tg. There were variations with sex and/or age for HDL2chol, HDL3chol, and HDL2Tg in the studied population., ((c) 2006 Wiley-Liss, Inc.)