Single Patient Use Research Articles

OPTIMUM DESIGN OF INTENSIVE CARE UNIT- AN EVIDENCE- BASED HEALING ENVIRONMENT

Successfully designing a new ICU requires clarity of vision and purpose and the recognition that the patient room is the core of the ICU experience for patients, staff, and visitors. The ICU canbe conceptualised into three components: the patient room, central areas, and universal support services. Each patient room should be designed for single patient use and be similarly configured and equipped. The design of the room should focus upon functionality, ease of use, healing, safety, infection control, communications, and connectivity. All aspects of the room, including itsinfrastructure; zones for work, care, and visiting; environment, medical devices, and approaches to privacy; logistics; and waste management, are important elements in the design process. Since most medical devices used at the ICU bedside are really sophisticated equipments, the ICU needs to be capable of supporting the full scope of medical informatics. The patient rooms, the central ICU areas (central stations, corridors, supply rooms, pharmacy, laboratory, staff lounge, visitor waiting room,) and the universal support services (infection prevention, finishings & and flooring, staff communications, signage & wayfinding, security and fire & safety) work best when fully interwoven. This coordination helps establish efficient and safe patient throughput and care and fosters physical and social cohesiveness within the ICU. Synchronisation of the universal support services in the ICU with the hospital’s existing systems maintains unity of purpose and continuity across the enterprise and avoids unnecessary duplication of efforts.

EPS9.09 Pilot study to evaluate the use of dry chlorine dioxide gas for sterilisation of virtual reality headsets

Objectives: Virtual Reality Headsets (VRH) are a developing part of patient care and virtual medicine, providing physical and psychological benefit to number of patients including pwCF. VRH are complex electronic devices incorporating different materials and there is a lack of robust and standardised decontamination protocols. VRH may be a potential source of infection transmission between patients which is particularly important in pwCF. One option is to restrict the use of VRH to single-patient use; however this limits their utility and increases cost. The aim of this study is to evaluate the use of dry chlorine dioxide (dClO2) gas with parametric validation as a standardized decontamination method for VRH.

Outbreak of Stenotrophomonas maltophilia infections in an intensive care unit—Alameda County, California, May–October 2022

Background:Stenotrophomonas maltophilia is a gram-negative, biofilm-producing bacterium that is ubiquitous in water environments and often associated with healthcare-associated infections (HAIs). Outbreaks of S. maltophilia bloodstream infections are a rare event and raise the suspicion of a common source. We used whole-genome sequencing (WGS) for an investigation of a cluster of S. maltophilia HAIs at a single hospital. Methods: A patient was defined as an intensive care unit (ICU) patient with fever and S. maltophilia isolated from a culture and who was treated for an HAI from May to October 2022. The response to the cluster included an epidemiologic investigation, water infection control risk assessments (WICRA), and environmental sampling. We also conducted WGS to characterize and assess relatedness between clinical and environmental S. maltophilia isolates. Results: From May 5 to October 1, 2022, we identified 11 HAIs due to S. maltophilia: 9 bloodstream infections and 2 ventilator-associated pneumonia cases. The initial epidemiological investigation did not identify common medical products, procedures, or personnel as an exposure source. The WICRA identified several breaches that may have exposed patients to contaminated water from sink backsplashes in the ICU, computerized tomography (CT) rooms, and the emergency department. In the CT rooms, saline bags were sometimes used for multiple patients, as were single-use intravenous contrast solution bottles. No additional cases were identified once infection control breaches were mitigated by installing sink splashguards, disinfecting drains, dedicating sink use for handwashing, and adhering to single-patient use of pharmaceutical products in the CT rooms. Of 46 environmental water samples, 19 were culture-positive for S. maltophilia. Isolates available for WGS included 7 clinical isolates (6 blood and 1 respiratory) and 17 environmental isolates. Among the 24 isolates sequenced, 16 unique multilocus sequence types (MLSTs) were identified. The 6 blood isolates sequenced were highly related (ST239, 0–4 high-quality, single-nucleotide variants [hqSNV] over 98.99% core genome), suggesting a common source. Two clusters of related environmental isolates were identified; however, overall MLST and hqSNV analyses suggested no relatedness between clinical and environmental isolates. Conclusions: An ICU cluster of S. maltophilia bloodstream infections was likely associated with water contamination of room surfaces and use of single-use intravenous products for multiple patients in the setting of a national pharmaceutical product shortage. This investigation highlights the importance of strong surveillance and water infection control, including routine assessment of ancillary areas in which intravenous products are administered and interdisciplinary collaboration to properly mitigate nosocomial transmission.Disclosures: None

Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers.

Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non-small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion-mediated osimertinib resistance has not previously been published. Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected. Fourteen patients with EGFR-mutant and RET fusion-positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%-75%, n = 12], 83% (95% CI, 55%-95%), and 7.9 months (range, 0.8-25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4-ALK/STRN-ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms. For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination. See related commentary by Krebs and Popat, p. 2951.

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Making Visible the Invisible: Automatically Measured Global and Regional Brain Volume Is Associated with Cognitive Impairment and Fatigue in Multiple Sclerosis.

In multiple sclerosis (MS), the transition from relapsing-remitting to the secondary-progressive phase is characterized by a progression independent of relapse activity (PIRA), resulting in physical disability accumulation and invisible symptoms, i.e., fatigue and cognitive impairment (CI). These symptoms are related to neurodegenerative processes and have been correlated with MRI measures of brain atrophy only at a group level; however, the application in clinical practice of atrophy-based measurements for single-patient evaluation is yet to be fully investigated. In the present study, we aimed to evaluate the association between brain atrophy, measured with easy-to-use automatic software, and the "invisible" MS symptoms of cognition and fatigue. A total of 69 MS patients were included in the study; cognitive impairment and fatigue (FSS) (in addition to neurological disability, EDSS) were assessed and correlated with brain volumes calculated using the automated software QyScore® which is validated for single-patient use in the clinical setting. Results showed that the cognitive status was accurately reflected by measures of atrophy, with a sensitivity of up to 90%. CI patients showed a lower volume compared to cognitively normal patients in the whole brain (p = 0.017), gray matter (p = 0.042), insula (p = 0.035), cerebellum (p = 0.008), and limbic lobe (p = 0.049). FSS was associated with temporal lobe (r = -0.37, p = 0.013) and insular (r = -0.36, p = 0.019) volumes. The volumes of the same regions were also associated with EDSS. The global/regional atrophy results, assessed with automatic and easy-to-use software, correlated with cognitive and fatigue symptoms, thus supporting the clinical application in routine patient management.

RAF-Independent MEK Mutations Drive Histiocytic Neoplasms In Vivo and Are Sensitive to Single-Agent ERK Inhibition in Patients

Histiocytic neoplasms are clonal disorders of the monocyte/macrophage lineage that include Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD). Histiocytoses are defined by recurrent, mutually exclusive mutations activating MAP kinase signaling, including BRAFV600E mutations in ~50% of LCH and ECD patients, which confer robust lasting clinical responses to BRAF inhibition. Mutations in MEK1/2, ARAF, and a diverse array of other kinases are present in BRAF wild-type histiocytoses patients and are broadly responsive to the allosteric MEK1/2 inhibitor cobimetinib. Following genomic analysis of ~300 pediatric and adult patients with diverse histiocytoses, the single most common genomic alteration following BRAFV600E mutations are MEK1 E102_I103 in-frame deletions. In contrast to BRAFV600E, the biological impact of activating mutations in MEK1/2 kinases are unknown, and no cancer associated MEK1/2 mutation has ever been modeled in vivo. MEK1/2 mutations are recurrent across a wide variety of human cancers and RASopathies and are now often found at resistance to emerging KRAS-mutant selective inhibitors. These findings motivated us to generate Map2k1E102_I103del conditional knock-in mice within the endogenous locus of Map2k1 (encoding MEK1 kinase), which represent the first genetically engineered mouse model of MEK1/2 mutations. We first crossed Map2k1E102_I103del mice to inducible Mx1-cre driver mice. Interestingly, Mx1-cre Map2k1E102_I103del knock-in mice developed a 100% penetrant lethal myelomonocytic disorder by 5-6 weeks of age while their cre-negative Map2k1E102_I103del littermates did not develop disease (Figure A). Notably, recombination of the Map2k1E102_I103del alleleoccurred spontaneously without pIpC administration and resulted in strong activation of phosphorylated ERK1/2 in bone marrow and spleen mononuclear cells. Mx1-cre Map2k1E102_I103del mice developed a myelomonocytic neoplasm with suppression of B-lymphopoiesis and expansion of classical and non-classical monocyte subsets, macrophages, and Cd11b+ conventional dendritic cells. Monocyte, macrophage, and dendritic cells infiltrated hematopoietic organs (bone marrow, spleen, and peripheral blood), as well as liver and skin, each of which are common sites of LCH and ECD disease involvement. The Mx1-cre Map2k1E102_I103del disease was hematopoietic cell autonomous and could be propagated by serial hematopoietic reconstitution in irradiated recipient mice, as well as using Vav1-cre Map2k1E102_I103del knock-in mice (where Cre is expressed only in hematopoietic cells from earliest hematopoietic development). Finally, restricting MEK1 mutant expression to monocyte and dendritic cell precursors using CD11c-cre resulted in similar lethal expansions of monocyte, macrophage, and dendritic cells as seen in the Mx1-cre and Vav1-cre models. Prior in vitro work has demonstrated that MEK1 p.E102_I103del activates MEK and ERK without requiring activated GTP-bound RAS and is associated with resistance to allosteric MEK inhibitors. Consistent with this, we identified nine histiocytosis patients with this specific MEK1 mutation, three of which had de novo resistance to cobimetinib. These three patients and one treatment-naïve patient were treated with an oral ERK1/2 inhibitor ulixertinib under the FDA single-patient compassionate use program. Three of 4 patients had a clinical or radiological partial or complete response to ulixertinib (Figure B). Overall, these data identify the impact of oncogenic MEK kinase mutations in vivo as found in children and adults with histiocytoses and RASopathies. Expression of a RAF-independent MEK1 mutation in vivo gave rise to disease reminiscent of human systemic histiocytic neoplasms. Importantly, this molecular entity is resistant to MEK inhibition in some patients, a phenomenon previously undocumented, but responsive to ERK inhibition, which may be a promising therapeutic approach to histiocytic neoplasms unresponsive to allosteric MEK inhibition. The clinical observation of efficacy of ERK inhibition in MEK inhibitor resistant histiocytoses patients has resulted in a soon-to-be initiated focused phase 2 clinical trial of ulixertinib in adults with histiocytoses. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pediatric Acute Myeloid Leukemia with Co-Occurring BCR::ABL and CBFA2T3::GLIS2 Dual Fusion with Deep Response to FOLR1-Targeting Antibody Drug Conjugate Stro-002 and Tyrosine Kinase Inhibitor

Introduction: Pediatric acute myeloid leukemia (AML) is characterized by significant cytogenetic and molecular heterogeneity. AML with CBFA2T3::GLIS2 fusion (CBF::GLIS) involving infants and very young children is a rare but uniformly refractory disease with high mortality. Laboratory data demonstrates that this fusion is sufficient for leukemic transformation without recurrent secondary variants. These studies have also linked CBF::GLIS fusion to induction of folate receptor alpha (FOLR1) expression in transformed cells (Meshinchi et al, 2020). Incidence of Ph+ de novo (BCR::ABL minor breakpoint, p190 hybrid) disease ranges from 0.5-3% of all AML cases across the age spectrum (Soupir et al, 2017). We, for the first-time, report dual existence of both fusions in a child with AML and discuss novel interventions including combination of a BCR::ABL tyrosine kinase inhibitor (TKI) and antifolate therapy consisting of methotrexate (MTX) and FLOR1-specific antibody-drug conjugate (ADC) STRO-002 (Sutro Biopharma) based on available data regarding its in-vitro preclinical activity in CBF::GLIS disease (Meshinchi et al, ASH abstract, 2021). Case: A 2-year-old girl of Vietnamese descent received a bone marrow examination for bicytopenia and macrocytosis. Flow cytometry confirmed the poor prognostic RAM immunophenotype AML (CD45 dim, HLA-DR negative, CD38 dim, CD56 bright) and FOLR1 expression. Marrow aspirate smears showed numerous hypercellular spicules and blasts with scant cytoplasm and some blebbing but no granules or Auer rods. Marrow exhibited 100% cellularity. CNS was not involved. Review of diagnostic genomic profile mid induction showed a BCR::ABL minor breakpoint fusion as well as CBF::GLIS fusion. The child began AML induction on COG AAML1831 trial randomized to the experimental arm with CPX-351 and gemtuzumab ozogamicin (GO). Due to lack of response to AML therapy at end of Induction (EOI) I, she was taken off protocol and started on modified ALL regimen for Induction II consisting of cytarabine, low dose weekly methotrexate and bimonthly peg-asparaginase with addition of an oral TKI, dasatinib. EOI II marrow examination showed improvement with reduction in blasts (11%) and detectable BCR::ABL but undetectable CBF::GLIS by Q-RT-PCR. Induction III included low dose weekly methotrexate, cytarabine, GO, and dasatinib. EOI III marrow examination showed complete morphologic remission (CR) with no evidence of minimal residual disease (MRD) or fusion transcripts of either clone. Due to availability of a matched sibling donor, the child underwent hematopoietic stem cell transplantation (HSCT); however, was noted to have 3% blasts on day +83 marrow examination despite previously commencing dasatinib post-transplant prophylaxis. BCR::ABL and CBF::GLIS transcripts were again detectable at low levels. Dasatinib dosage was maximized and weekly MTX and bimonthly peg-asparaginase were reintroduced, but the marrow disease burden increased significantly to 78% blasts positive only for CBF::GLIS fusion. Given availability of FOLR1 directed ADC on single-patient compassionate use basis, patient received single agent STRO-001 on a bi-monthly basis. With rising ANC, evaluation of marrow after 2nd STRO-002 dose remarkably showed CR with MRD negative remission by flow and molecular studies. This time remission was consolidated with monthly STRO-002 and donor lymphocyte infusions (DLI). Currently, patient remains in MRD-negative remission after the 3 of 4 planned STRO-002/DLI maintenance. Patient has maintained a 100% Lansky play score and tolerated the regimen with only prolonged initial cytopenia requiring supportive care as a toxicity. Plan is to continue TKI and monthly STRO-002 as maintenance therapy. Conclusion: Complete genomic sequencing has revolutionized pediatric AML categorization. It is quite conceivable that (BCR::ABL, CBF::GLIS) dual fusion disease will become a more common finding in future. Although CBF::GLIS AML is uniformly refractory to conventional therapy, targeted therapy with FOLR1-directed STRO-002 was highly effective in eliminating CBF::GLIS clone in this patient, and combination with DLI appears to be feasible. Long-term follow-up is required to assess durability of remission. Additional testing of this approach in a larger patient population is needed to determine the role of STRO-002 in this high-risk pediatric AML population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

7% sodium citrate (with benzyl alcohol) as catheter lock: Dedication or obsession?

The standard heparin lock for dialysis catheters in US dialysis units is 1000 units/ml, though its use has significant limitations and problems. The alternative catheter lock of 4% sodium citrate is used in some patients, but a 7% solution would maintain catheter patency better than the 4% concentration. In spite of the failure of two prior catheter locks to become widely used in the US (highly concentrated citrate and Zuragen™), Ash Access worked with a compounding pharmacy to produce 7% sodium citrate with preservative in single-patient use frangible vials, at a reasonable cost to users. The product had early acceptance by a number of dialysis units and hospitals, but then follow-up orders were few. Where the project goes from here is unclear.

Potential Cost Savings Associated with a Multiuse Preoperative and Preinjection Eyedrop Protocol

To calculate the cost savings associated with a multiuse preoperative and preinjection eyedrop protocol. Economic analysis. Adults undergoing ophthalmic surgical procedures requiring preoperative dilation and intravitreal injections. Economic modeling with scenario analysis was used to derive the value for cost savings secondary to a protocol in which perioperative mydriatic eyedrop bottles are used across multiple patients versus the current protocol in which drop bottles are wasted after single-patient use. Similar analyses were performed for a multiuse povidone-iodine protocol for intravitreal injections. Sensitivity analyses were used to test baseline model assumptions with varying degrees of waste and patient volume. The multiuse mydriatic protocol allowed for a 97.1% reduction in the number of eyedrop bottles required for the single-use protocol (1037 bottles vs. 35 850 bottles). This led to an estimated 5-year cost savings of approximately $240 000 (nominal) per institution (performing an average of 1434 cases/year) in the base case. This savings varied minimally in sensitivity analyses accounting for practical limitations (loss, expiration, or contamination) of multiuse containers, with savings of 97.54% to 95.00% for excess supply ranges from 0% to 100% in the multiuse protocol. Likewise, the cost savings varied minimally in sensitivity analyses for eyedrop sizes, with savings of 99.23% to 96.69% for mydriatic eyedrop sizes of 15 μl per drop to 65 μl per drop, respectively, in the multiuse protocol. Over a 5-year period, for povidone-iodine drops before performing intravitreal injection, the multiuse protocol required 153 bottles compared with 41 954 bottles (99.6% reduction) for the current single-use protocol, resulting in a nominal cost savings of $41 801, which varied minimally in sensitivity analyses. Multiuse perioperative mydriatic eyedrops are a viable option for cost and environmental waste reduction for ophthalmologic procedures and surgeries requiring dilation. Likewise, multiuse povidone-iodine may allow for large relative cost reduction for in-office procedures. The total potential savings over 5 years was estimated at more than $280 000 before adjusting for inflation.

Decreasing insulin wastage in acute medical assessment units at Hamad General Hospital

Background: Insulin therapy is commonly used to control hyperglycemia in hospitalized diabetic patients. There are different delivery devices of Aspart and Glargine insulin which are available in 1000 IU vial and 300 IU Flexpen. As per the manufacturer's recommendations, insulin pre-filled pens are designed for single patient use only, whereas the vial form is intended for multidose administration for different patients, therefore, the selection amongst both forms of insulin will certainly impact the consumption cost. According to our observation, there was an unjustified prescribing discrepancy between both forms. Several studies have shown a decrease in insulin wastage associated reduction in acquisition costs when switching from pre-filled pens to vials1-3. Methods: This is a quality improvement project that aims to enhance prescribing insulin vials in acute medical units at Hamad General Hospital. Insulin consumption data were retrospectively reviewed between July 2020-May 2021. Data were obtained 3 months consecutively at baseline and post improvement interventions which consist of 2 steps. Step 1: educating physicians and nurses about the cost effectiveness of insulin delivery devices, and Step 2: Transitioning patients from insulin Flexpen to vials by an authorized pharmacist. The outcomes measures were related to insulin consumption and cost reduction. The process was measured by the amount of Flexpens dispensed. Results: From July-October 2020, 400 patients consumed 81500 IU of insulin Aspart and 58600 IU of insulin Glargine, with a total number of 297 Flexpens used. After implementing improvement intervention, insulin consumption for 551 patients from February – May 2021 reduced to 19200 IU (76.4%) for Aspart and 18900 IU (67.7%) Glargine (Figure 1), comparing with same interval period only 38 Flexpens were dispensed. Economically, the transition to insulin vials reduced the hospital cost by 71% (Table 1). Conclusion: Compared to Flexpen, insulin vial prescribing in hospitalized diabetic patients led to waste and cost consumption reduction of insulin.

Intubation using VieScope vs. Video laryngoscopy in full personal protective equipment \u2013 a randomized, controlled simulation trial

BackgroundVieScope is a new type of laryngoscope, with a straight, transparent and illuminated blade, allowing for direct line of sight towards the larynx. In addition, VieScope is disposed of after single patient use, which can avoid cross-contaminations of contagious material. This has gained importance especially when treating patients with highly contagious infectious diseases, such as during the SARS-CoV2 pandemic. In this context, VieScope has not been evaluated yet in a clinical study.Material and methodsThis study compared intubation with VieScope to video-laryngoscopy (GlideScope) in normal and difficult airway in a standardized airway manikin in a randomized controlled simulation trial. Thirty-five medical specialists were asked to perform endotracheal intubation in full personal protective equipment (PPE). Primary endpoint was correct tube position. First-pass rate (i.e., success rate at the first attempt), time until intubation and time until first correct ventilation were registered as secondary endpoints.ResultsFor correct tracheal tube placement, there was no significant difference between VieScope and GlideScope in normal and difficult airway conditions. VieScope had over 91% fist-pass success rate in normal airway setting. VieScope had a comparable success rate to GlideScope in difficult airway, but had a significantly longer time until intubation and time until ventilation.ConclusionVieScope and GlideScope had high success rates in normal as well as in difficult airway. There was no unrecognized esophageal intubation in either group. Overall time for intubation was longer in the VieScope group, though in an acceptable range given in literature.Results from this simulation study suggest that VieScope may be an acceptable alternative for tracheal intubation in full PPE.Trial RegistrationThe study was registered at the German Clinical Trials Register www.drks.de (Registration date: 09/11/2020; TrialID: DRKS00023406).

Joint Healthcare Infection Society (HIS) and Infection Prevention Society (IPS) guidelines for the prevention and control of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities

Joint Healthcare Infection Society (HIS) and Infection Prevention Society (IPS) guidelines for the prevention and control of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities

Multicenter Analysis of Genomically Targeted Single Patient Use Requests for Pediatric Neoplasms.

The US Food and Drug Administration-expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer. All genomically targeted therapeutic SPUs obtained over a 5-year period were evaluated at four large pediatric cancer programs. Data were collected on the type of neoplasm, agents requested, corresponding molecularly informed targets, and clinical outcomes. A total of 45 SPUs in 44 patients were identified. Requests were predominantly made for CNS and solid tumors (84.4%) compared with hematologic malignancies (15.6%). Lack of an available clinical trial was the main reason for SPU initiation (64.4%). The median time from US Food and Drug Administration submission to approval was 3 days (range, 0-12 days) and from Institutional Review Board submission to approval was 5 days (range, 0-50 days). Objective tumor response was seen in 39.5% (15 of 38) of all evaluable SPUs. Disease progression was the primary reason for discontinuation of drug (66.7%) followed by toxicity (13.3%). SPU requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of SPUs resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of SPUs may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.

EPCT-10. DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN RECURRENT/REFRACTORY FGFR ALTERED PEDIATRIC GLIOMAS

BackgroundOncogenic driver alterations in FGFR are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor that had a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study. MethodsFive children with progressive/refractory CNS tumors harboring an FGFR gene alteration following prior therapy were treated with Debio1347 at Memorial Sloan Kettering Cancer Center on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 * BSA once daily). Toxicities were graded using CTCAEv5.0 and imaging response assessments were performed every 8–12 weeks. RESULTS All AEs were grade 1–2. Most common treatment-related adverse events were hyperphosphatemia, ALT increased and hypoalbuminemia (4 patients). Two patients met criteria for partial response and two patients had stable disease. A 13 month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations (V592M, K687E) had tumor reduction of 91.7% maintained for 12 months. A 26-month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Molecular characterization of recurrent tumor from this patient demonstrated an NF1 deletion as a novel molecular mechanism of acquired resistance to FGFR inhibition. Prolonged disease stabilization was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring an FGFR1 mutation (9 months) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (24 months and ongoing). ConclusionsDebio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with refractory FGFR altered gliomas. Specific attention to growth velocity and clinical symptoms with incorporation of imaging assessment of bone growth is warranted. Candidate biomarkers (FGFR1 V592M and K687E SNVs, FGFR-TACC fusions) may guide patient selection. Further studies in this population are warranted.

EPCT-07. DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN RECURRENT/REFRACTORY FGFR ALTERED PEDIATRIC GLIOMAS

BACKGROUNDOncogenic driver alterations in FGFR are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor that had a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study.METHODSFive children with progressive/refractory CNS tumors harboring an FGFR gene alteration following prior chemotherapy were treated with Debio1347 at Memorial Sloan Kettering Cancer Center on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 * BSA once daily). Toxicities were graded using CTCAEv5.0 and imaging response assessments were performed every 8–12 weeks.RESULTSAll AEs were grade 1–2. Most common treatment-related adverse events were ALT increased, hypoalbuminemia and hyperphosphatemia (4 patients). Two patients met criteria for partial response and two patients had stable disease. A 13 month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations (V592M, K687) had tumor reduction of 91.7% maintained for 12 months. A 26-month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Prolonged disease stabilization was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring an FGFR1 mutation (9 months) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (18 months and ongoing).CONCLUSIONSDebio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with refractory FGFR altered gliomas. Further studies in this population are warranted.

CTNI-33. DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN PEDIATRIC PATIENTS WITH RECURRENT/REFRACTORY FGFR ALTERED GLIOMAS

Abstract BACKGROUND Oncogenic driver alterations in fibroblast growth factor receptors (FGFRs) are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor with a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study. METHODS We treated five children with progressive/refractory CNS tumors harboring an FGFR gene alteration with Debio1347 on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 ′ BSA once daily). RESULTS All adverse events (AEs) were grade 1–2. Most common treatment-related AEs were hyperphosphatemia, ALT elevation and hypoalbuminemia. Two patients met criteria for partial response and two patients had stable disease. A 13-month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations had tumor reduction of 96.3% maintained for 11 months. A 26 month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Prolonged disease stabilization and clinically significant improvement in visual function was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring two FGFR1 mutations (14 months overall and sustained for 6 months off therapy) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (26 months and ongoing). CONCLUSIONS FGFR targeted therapy with Debio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with recurrent/refractory FGFR altered gliomas. Further studies in this population are warranted.

ISMP updates: Remdesivir, propofol, and vincristine

ISMP updates: Remdesivir, propofol, and vincristine

Abstract A50: Targeted therapies for children and young adults with cancer: Single-patient use (SPU) experience at three large pediatric cancer programs

Abstract Introduction: The Food and Drug Administration (FDA) expanded access program uses a single-patient use (SPU) mechanism to provide patient access to investigational agents prior to FDA approval and outside clinical trials, in situations where no satisfactory or comparable therapy is available. Genomic profiling of both newly diagnosed and relapsed/refractory childhood cancer has increased in the last decade, resulting in identification of new drug targets for pediatric malignancies. Recently, a review of SPU use in adult and pediatric patients at a single institution (Feit, JAMA Oncology 2019) showed that a markedly higher percentage of pediatric patients receive access through SPUs compared with adult patients, identifying this as an important means of pediatric drug access. However, little is known about the pediatric use and efficacy of SPUs in children. The aim of this study is to examine the SPU experience in pediatric and adolescent and young adult (AYA) cancer patients—specifically obtained for targeted therapies at three large pediatric cancer centers. Methods: All therapeutic SPUs obtained between January 1, 2014 and January 1, 2019 were evaluated at the Aflac Cancer & Blood Disorders Center (Atlanta, GA), Cincinnati Children’s Hospital (Cincinnati, OH), and the Memorial Sloan Kettering Cancer Center (New York, NY). Data were collected on the type of malignancy, agents requested, and corresponding molecularly informed targets, if applicable. Results: A total of 61 SPUs were approved in the five-year period, with 34 (55%) of them specific for access to agents based on somatic tumor mutations identified by genomic profiling. Among the disease groups, SPUs were most often requested for tumors affecting the central nervous system (CNS) (48%), followed by solid tumors (bone, liver, and kidney tumors) (26%), hematologic malignancies (leukemia/lymphoma) (21%), and other rare tumors (5%). Kinase inhibitors were the most frequently requested agents in the genomically defined category (n=34), specifically, FGFR (fibroblast growth factor receptor) inhibitors followed by drugs targeting NTRK 1/2/3 (tropomyosin receptor kinase (Trk) receptors). Most patients within this genomically targeted group (18/34) are currently receiving therapy with these agents. Conclusions: We found that SPUs represent an important means of access to therapeutic agents in the pediatric and AYA populations, with more than half of all SPUs based on rearrangements identified by genomic profiling. A broad range of agents were requested across CNS, solid tumor, and hematologic types. Furthermore, more than half of the patients remain on their respective SPU-approved drug. We are currently performing a more detailed analysis of clinical responses, as well as a time analysis from SPU initiation to approval for all patients in this cohort. Establishment of this cohort of patients across institutions will serve as the basis for a formal registry of pediatric SPUs, which will enable us to study their use and efficacy over time. Citation Format: Himalee Sabnis, Benjamin Mizukawa, Julia Glade-Bender, Jason Fangusaro, Stephen Roberts, Chanta Whitlow, Marilyn Winchester, Maureen O’Brien, Laura Agresta, Brian Turpin, Daniel Wechsler, Sharon Castellino, Neerav Shukla. Targeted therapies for children and young adults with cancer: Single-patient use (SPU) experience at three large pediatric cancer programs [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A50.

The Vacuum Assisted Negative Pressure Isolation Hood (VANISH) System: Novel Application of the Stryker Neptune™ Suction Machine to Create COVID-19 Negative Pressure Isolation Environments.

Coronavirus disease 2019 (COVID-19) may remain viable in the air for up to three hours, placing health care workers in close proximity to aerosolizing procedures particularly at high risk for infection. This combined with the drastic shortage of negative pressure rooms hospitals worldwide has led to the rapid innovation of novel biohazard isolation hoods, which can be adapted to create negative pressure isolation environments around the patient's airway using the hospital wall suction, which carries many limitations, including weaker suction capabilities, single patient use, and immobility. Here, we report our Vacuum Assisted Negative Pressure Isolation Hood (VANISH) system that uses a mobile and readily available in most hospital operating rooms Stryker Neptune™ (Stryker Corporation, Kalamazoo, Michigan) high-powered suction system to more effectively create a negative pressure biohazard isolation environment. VANISH has been utilized regularly in an anesthesia practice of 30+ providers and, to date, there have been no documented COVID-19 infections.