Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma.

Fludarabine/cyclophosphamide (Flu/Cy) is established for lymphodepletion (LD) prior to standard-of-care CAR T-cell therapy for lymphoma. There is ongoing need to test alternative LD regimens to preserve efficacy, improve safety, and address challenges including the recent national fludarabine shortage. We retrospectively evaluated outcomes among patients with relapsed/refractory aggressive B-cell lymphoma who received bendamustine (n = 27) or Flu/Cy (n = 42) LD before axicabtagene ciloleucel (axi-cel) at our institution. The median change in absolute lymphocyte count from pre-LD to time of axi-cel infusion was -0.6×109 /L in bendamustine cohort and -0.7×109 /L in Flu/Cy cohort. The best overall response/complete response rates were 77.8% (95% CI: 57.7%-91.4%)/48.1% (95% CI: 28.7%-68.1%) among bendamustine cohort and 81.0% (95% CI: 65.9%-91.4%)/50.0% (95% CI: 34.2%-65.8%) among Flu/Cy cohort. Six-month progression-free survival were 43.8% (95% CI: 24.7%-61.3%) and 55.6% (95% CI: 39.0%-69.3%) in bendamustine and Flu/Cy cohorts, while 6-month overall survival were 81.5% (95% CI: 61.1%-91.8%) and 90.4% (95% CI: 76.4%-96.3%), respectively. Relative to Flu/Cy-treated patients, bendamustine-treated patients did not show an increase in hazards associated with experiencing progression/relapse/death (aHR:1.4 [95% CI: 0.7-2.8]; p = .32) or death (aHR:1.6 [95% CI: 0.5-5.6]; p = .46), after adjusting for baseline number of prior therapies and refractory disease. Any grade/grade ≥3 CRS were observed in 89%/3.7% and 86%/4.8% among bendamustine and Flu/Cy cohorts, while any grade ICANS/grade ≥3 ICANS were observed in 30%/19% and 55%/31% respectively. While more Flu/Cy-treated patients experienced grade ≥3 neutropenia compared with bendamustine-treated patients (100% vs. 68%), grade ≥3 infectious complications were comparable (24% vs. 19% respectively). More patients received bendamustine LD and axi-cel as outpatient than Flu/Cy cohort, without increased toxicities and with shorter median inpatient stays. In conclusion, we observed comparable efficacy and lower any grade ICANS among patients receiving bendamustine relative to Flu/Cy LD, followed by axi-cel.

Polycaprolactone-based fused deposition modeled mesh for delivery of antibacterial agents to infected wounds.

Infections represent a significant source of site morbidity following tissue trauma. Scarring and tissue adhesion remain the challenging issues yet to be solved. Prolonged inflammation and morphology of the re-epithelisated layer are important considerations. We hypothesized that the solution lies not only in the biochemistry of biomaterial but also the micro-architecture of the scaffold used as the matrix for wound healing. Targeted delivery of antibiotics may provide an efficacious means of infection control through adequate release. Here, we study the use of 3-dimensional polycaprolactone-tricalcium phosphate (PCL-TCP) mesh for the delivery of gentamicin sulphate (GS) fabricated using a solvent-free method. PCL-TCP meshes incorporated with varying loads of GS were evaluated in vitro for elution profile, antimicrobial efficacy and cytotoxicity. Results showed that PCL-TCP meshes incorporated with 15 wt% GS (PT15) efficiently eliminate bacteria within 2 h and demonstrate low cytotoxicity. Subsequently, PT15 meshes were evaluated using an infected full thickness wound mice model, and observed to eliminate bacteria in the wounds effectively. Additionally, mice from the PT15 treatment group (TG) showed no observable signs of overall infection through neutrophil count by day 7 and displayed efficient wound healing (94.2% wound area reduction) by day 14. Histology also showed significantly faster healing in TG through neo-collagen deposition and wound re-epithelisation. The meshes from TG were also observed to be expelled from wounds while gauze fibers from CG were integrated into wounds during healing.