Canossa Private Hospital

7514 Background: MM remains an incurable disease and resistance mechanisms are emerging. ISB 2001, a first-in-class trispecific T cell engager, redirects cytotoxic T cells to BCMA and/or CD38-expressing myeloma cells. By simultaneously targeting two TAA, ISB 2001 enhances avidity binding to tumor cells in vitro, hence potency, while the distal positioning of the CD38 vs CD3 binders minimizes CD38-related off-tumor adverse events. Methods: We report data from the DE portion of a Phase 1 study of ISB 2001, assessing safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) in RRMM patients (pts) exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 therapies and refractory or intolerant to established therapies. Prior BCMA-targeted and/or T-cell directed therapies were allowed. ISB 2001 was administered weekly subcutaneously (SC) in 28-day cycles, with initial step-up doses on Days 1 (15µg/kg) and 4 (variable). DE utilized an accelerated titration design (initial 3 cohorts with single-patient dosing) followed by a standard 3+3 design. DLTs were evaluated in the first 28 days. After DE, the study will proceed with Part 2 (dose expansion) to confirm safety and select the recommended Ph2 dose under FDA Project Optimus. Results: As of January 13, 2025, 24 pts were treated with ISB 2001 across 8 dose levels (5–1800 μg/kg) with a median follow-up of 6 months (range: 2–12). DL9 (2700 µg/kg) is last dose level and currently enrolling. Among 24 pts, median age was 66 years; 58% male, 83% white with a median of 6 prior lines of therapy (range: 3-11). All pts were triple-exposed, 17/24 (71%) penta-exposed, and 3/17 penta-refractory (18 %). No DLT, adverse events (AE) leading to treatment discontinuation or deaths occurred. Serious AEs were reported in 8 (33%) patients. Drug related Grade (Gr) 3-4 AEs were seen in 13 (54%) pts. CRS was reported in 17 (70.8%) patients, primarily Grade 1–2, with a median onset of 3 days and a median duration of 2 days. No neurologic AEs or ICANs. The Overall Response Rate (ORR) was 75% across all 8 doses, including stringent CR (sCR) 13%, CR 13%, VGPR 38%, PR 13%. Responses were observed from dose level as low as 50 µg/kg (MRD-neg, sCR) with an ORR of 82% at doses ≥50 µg/kg. Median time to response was 36 days. ISB 2001 showed near dose-proportional PK, a half-life >10 days, and consistent T-cell activation, supporting its mechanism of action. Conclusions: ISB 2001 was well tolerated with manageable CRS, no ICANS and demonstrated robust anti-myeloma activity in heavily pretreated RRMM pts (NCT05862012). Full clinical data, including PK and PD results from the dose-escalation portion of the study, will be presented at the conference. Clinical trial information: NCT05862012 .

Background and objectiveAn epidemic of silicosis has emerged due to a failure to control risks associated with exposure to high‐silica content respirable dust generated while working with artificial stone products. Methods for quantification of alveolar crystal burden are needed to advance our understanding of the pathobiology of silica‐related lung injury as well as assisting in the diagnosis, clinical management and prognostication of affected workers. The objective of this study was to develop and validate novel methods to quantify alveolar crystal burden in bronchoalveolar lavage (BAL) fluid from patients with artificial stone silicosis.MethodsNew methods to quantify and analyse alveolar crystal in BAL from patients with artificial stone silicosis were developed. Crystals were isolated and counted by microscopy and alveolar crystal burden was calculated using a standard curve generated by titration of respirable α‐Quartz. The utility of the assay was then assessed in 23 patients with artificial stone silicosis.ResultsAlveolar crystal burden was greater in patients with silicosis (0.44 picograms [pg]/cell [0.08–3.49]) compared to patients with other respiratory diagnoses (0.057 pg/cell [0.01–0.34]; p < 0.001). Alveolar crystal burden was positively correlated with years of silica exposure (ρ = 0.49, p = 0.02) and with decline in diffusing capacity of the lungs for carbon monoxide (ρ = −0.50, p = 0.02).ConclusionAlveolar crystal burden quantification differentiates patients with silicosis from patients with other respiratory disorders. Furthermore, crystal burden is correlated with the rate of decline in lung function in patients with artificial stone silicosis.

Conducting spinal anaesthesia in patients with elevated body mass index is commonly difficult, yet there are no guidelines to direct best practice. Landmark techniques are sometimes insufficient, leading to increased failure rates and suboptimal patient outcomes. Although ultrasound-guided techniques are now considered standard care for central venous access and regional anaesthesia, there has been relatively sparse uptake of this widely available resource for central neuraxial block, despite evidence of its efficacy.This article outlines a successful case of ultrasound-assisted spinal anaesthesia, after landmark techniques failed, in conjunction with a combined spinal-epidural kit. This unique combination of techniques has not been published as an amalgamated rescue strategy for difficult spinal anaesthesia. This article adds to current evidence by highlighting the potential benefits of combining these techniques into a novel approach either when difficulties are expected or as a rescue technique after failed landmark-based attempts.

Background: The Australian Lymphoedema Education, Research and Treatment Program (ALERT) at Macquarie University in Sydney, Australia is one of the flagship programs of Australia's first fully integrated academic health sciences centre, MQ Health. The aim of this study was to describe our findings of compensatory drainage demonstrated by indocyanine green (ICG) lymphography in cancer-related upper and lower limb lymphedema and how this may be translated into clinical practice. Methods and Results: Retrospective data from 339 patients aged between 18 and 90 years with secondary cancer-related unilateral or bilateral lymphedema of the upper or lower limb who underwent ICG lymphography assessment at the ALERT clinic between February 2017 and March 2020 were analyzed. In patients with upper limb lymphedema, the ipsilateral axilla was the most frequent drainage region (74.9%), followed by clavicular (41.8%) and parasternal (11.3%). For patients with mild upper limb lymphedema, 94.4% drained to the ipsilateral axilla. No patients drained to the ipsilateral inguinal region. For lower limb lymphedema, drainage to the ipsilateral inguinal was most common (52.3%), followed by contralateral inguinal (30.7%), popliteal (26.1%), and gluteal (21.6%) regions. Three main patterns of superficial lymphatic compensation were identified based on which anatomical structure carried lymph fluid. Manual lymphatic drainage (MLD) was used to facilitate movement of the dye. A light/effleurage technique was sufficient to move the dye through patent lymphatic vessels; a slow and firmer technique was required to move the dye through areas of bridging dermal backflow. Conclusion: The introduction of ICG lymphography to our program and its use in guiding personalized conservative management plans, including facilitative MLD techniques, has translated into clinical practice and changed research and educational priorities within the ALERT program.

Abstract Methotrexate is a cytotoxic agent that is commonly used to treat autoimmune diseases, and both solid and hematological malignancies. Drug interactions are of particular concern during methotrexate therapy, as they have the potential to alter the pharmacokinetics of methotrexate and lead to significant toxicity. One agent that has the potential to interact with methotrexate is the antimicrobial agent trimethoprim with sulfamethoxazole. Consideration of this interaction is of importance in patients that are undergoing high‐dose methotrexate therapy for hematological malignancies as trimethoprim/sulfamethoxazole is the preferred agent for Pneumocystis jiroveci pneumonia prophylaxis. Current Australian guidelines recommend avoiding concurrent administration of high‐dose methotrexate and trimethoprim/sulfamethoxazole, yet evidence to support this recommendation is unclear. This review investigates the current available evidence that focuses on the interaction between high‐dose methotrexate and trimethoprim/sulfamethoxazole and aims provide guidance for the use of this combination in clinical practice.