Impact of debulking therapy on the clinical outcomes of axicabtagene ciloleucel in the treatment of relapsed or refractory large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, was approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the results from pivotal Cohorts 1+2 of ZUMA-1 (NCT02348216). ZUMA-1 was expanded to investigate safety management strategies aimed at reducing the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs). Prospective safety expansion Cohort 5 evaluated the impact of debulking therapy, including rituximab-containing immunochemotherapy regimens and radiotherapy, in axi-cel-treated patients; the CRS and NE management strategy paralleled those in Cohorts 1+2.

Long-term outcomes of patients with large B-cell lymphoma treated with axicabtagene ciloleucel and prophylactic corticosteroids.

ZUMA-1 safety management cohort 6 investigated the impact of prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab on the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs) following axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Prior analyses of cohort 6 with limited follow-up demonstrated no Grade ≥3 CRS, a low rate of NEs, and high response rates, without negatively impacting axi-cel pharmacokinetics. Herein, long-term outcomes of cohort 6 (N = 40) are reported (median follow-up, 26.

Axicabtagene Ciloleucel in Combination with the 4-1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11.

Purpose: Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4-1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy.

Patients And Methods: In phase 1 of the single-arm ZUMA-11 trial, patients with R/R LBCL received a single axi-cel infusion (target dose, 2 × 106 cells/kg) plus utomilumab 10 to 200 mg intravenously every 4 weeks for up to 6 months in a dose-escalation design.

Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody-Drug Conjugates.

AGS-16C3F is an antibody-drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. AGS-16C3F and other ADCs have been reported to cause ocular toxicity in patients by unknown mechanisms. To investigate this toxicity, we developed an assay using human corneal epithelial cells (HCEC) and show that HCECs internalized AGS-16C3F and other ADCs by macropinocytosis, causing inhibition of cell proliferation.

Oscar Wilde's skin disease: allergic contact dermatitis?

During the last years of his life, Oscar Wilde (1856-1900) suffered from a suppurating otitis media as well as from an unidentified skin disease. The eruption was localized to his face, arms, chest and back and itched severely. A new theory is suggested, based on the fact that Wilde almost certainly used a dye to conceal his rapidly graying hair.

Evaluation of a self-administered questionnaire on hand dermatitis.

The purpose of the study was to evaluate a self-administered questionnaire on hand dermatitis that was developed to identify persons with hand dermatitis in epidemiological studies. A total of 109 nurses were subject to dermatological examination of the hands within 1 month of returning the questionnaire. 2 types of questionnaire diagnoses were made: a 'symptom-based' diagnosis and a 'self-reported diagnosis'.

Patch tests with house dust mite antigens in atopic dermatitis patients: methodological problems.

Patch tests with house dust mite allergens were performed in 21 atopic dermatitis patients with a positive prick test and RAST for house dust mite. Variables in methodology of patch testing, i.e.

Susceptibility to irritants: role of barrier function, skin dryness and history of atopic dermatitis.

The susceptibility of the skin to various irritants was investigated with the aim of determining the role of the barrier function of the stratum corneum, skin dryness and whether a history of atopic dermatitis (AD) was a factor. The transepidermal water loss (TEWL) was measured using an evaporimeter and skin hydration using a Corneometer and by visual scoring. The group with a history of AD (n = 20) had a lower pre-exposure barrier function and a higher TEWL value following irritant exposure than the group with a history of allergic contact dermatitis (n = 18) and a control group (n = 18).

Evaluation of detergent-induced irritant skin reactions by visual scoring and transepidermal water loss measurement.

Transepidermal water loss measurements proved to be more accurate and sensitive than visual scoring in discriminating the irritating action of detergents on the skin. Further, the baseline transepidermal water loss might be a reliable indicator of an individual's susceptibility to weak irritants.

Variability in transepidermal water loss of the skin: evaluation of a method to assess susceptibility to contact dermatitis in epidemiological studies.

Transepidermal water loss (TEWL) has been suggested to be a measure which can be used to identify subjects at risk for the development of contact dermatitis. Transepidermal water loss is high when the barrier function of the skin is impaired. It is assumed that subjects with a high TEWL have skin which is more permeable to substances causing contact dermatitis.

The transient and cumulative effect of sodium lauryl sulphate on the epidermal barrier assessed by transepidermal water loss: inter-individual variation.

The aims of the investigation were: 1) to study the inter-individual variation in time course of TransEpidermal Water Loss and of clinical manifestations after a 24-h single exposure to Sodium Lauryl Sulphate. This TEWL time course (expressed as the difference in TEWL between the day of patch removal and a subsequent day) reflected the epidermal barrier response to the damage caused by SLS; 2) to investigate the association between the TEWL time course after the single SLS exposure and the TEWL value after 4-day repeated SLS exposure (as a model for cumulative irritation). The 35 healthy subjects tested could be divided into four sub-groups according to the day of their maximum TEWL value after the single SLS exposure (days 2 to 5).

The intra- and inter-individual variability and reliability of transepidermal water loss measurements.

An analysis of variance was conducted to estimate the intra- and inter-individual variations in TEWL on the forearms, by sites (8 measurement sites) and by days (10 different days), in 30 non-exposed healthy individuals. The estimated intra- and inter-individual variations, by sites, were 15.5% and 84.

Transepidermal water loss with and without sweat gland inactivation.

The influence of eccrine sweating on transepidermal water loss (TEWL) was investigated. TEWL was simultaneously measured on both forearms, with and without topical inactivation of the eccrine sweat glands by 0.3 ml of 0.

Prediction of susceptibility to an irritant response by transepidermal water loss.

The roles of the natural permeability of the stratum corneum to water, and the changes in that permeability effected by a single patch test, were investigated as parameters to predict the susceptibility of the skin to repeated exposures of an irritant. One site on the forearm skin of 27 non-atopic healthy subjects was exposed to a 0.5% concentration of sodium lauryl sulphate by a single occlusive 24-h patch.

Baseline transepidermal water loss (TEWL) as a prediction of susceptibility to sodium lauryl sulphate.

The rôle of different factors in the susceptibility of the skin to weak irritants was studied by means of multiple linear regression models. The skin of 37 healthy subjects was exposed to a solution of sodium lauryl sulphate of low molarity 2 x daily for 4 days. The condition of the skin was evaluated by transepidermal water loss (TEWL) measurements on the 1st day (before exposure, TEWL1) and on the 5th day of exposure (TEWL5), and by a visual scoring system.

Comparability and reproducibility of the results of water loss measurements: a study of 4 evaporimeters.

A study was made of the comparability and reproducibility of the results of measurements of water loss, both in vitro and in vivo, using 4 ServoMed Evaporimeters (3 single-probe and 1 double-probe instrument). The optimum time for recording transepidermal water loss (TEWL) after the initial application of the probe to the skin (in vivo), and the best technique for optimizing the accuracy of measuring TEWL were determined. An evaporation device with a constant level of water loss was constructed for in vitro studies.

The influence of repeated exposure to surfactants on the human skin as determined by transepidermal water loss and visual scoring.

The purpose of this study was to develop a new model for the induction of chronic irritant contact dermatitis, which would reflect well the conditions of daily practice. Various weak irritant agents were tested for irritating potency on the skin and the sensitivity of transepidermal water loss (TEWL) measurements in the detection of early skin changes was also studied. 10 widely used surfactants and 1 solubilizer were applied to the skin of the forearms of healthy volunteers in aqueous solutions of 12.

Maculopapular rash due to coumarin derivatives.

The case history is presented of a patient who developed a maculopapular rash following treatment with 3 different coumarin derivatives. Apparently cross-sensitivity between coumarin derivatives may occur.

The role of contact allergy in the spectrum of adverse effects caused by cosmetics and toiletries.

Of 982 female clients of beauticians interviewed, 254 (25.9%) claimed to have experienced adverse reactions to cosmetics and toiletries in the preceding 5 years. Most reactions were caused by skin-care products (36.