The 50th annual meeting of the european society for blood and marrow transplantation: pharmacist committee – poster session (p762-p770)

You have full access to this article via your institution. Download PDF 14–17 April, 2024 ● Hybrid Meeting COPYRIGHT: Modified and published with permission from

https://www.ebmt.org/annual-meeting SPONSORSHIP STATEMENT: The publication of this supplement is sponsored by the European Society for Blood and Marrow Transplantation. All content was

reviewed and approved by the EBMT Committee, which held full responsibility for the abstract selections. PHARMACOLOGY POSTER SESSION 36: PHARMACOLOGY P762 ANTI-POLYOMAVIRUS CELLULAR

IMMUNOTHERAPY: AN INNOVATIVE THERAPY IN FOUR PATIENTS WITH POLYOMAVIRUS INFECTIONS ALEXANDRE CHEVALIER1, GUILLAUME MARTIN-BLONDEL2, ANNE-BÉATRICE NOTARANTONIO1,3, SIMONA PAGLIUCA1,3, MARIE

THÉRÈSE RUBIO1,3, JEAN-JACQUES TUDESQ4, AGATHE ARTIAGA4, DAVIDE STRAMBO5, PASCAL LEJEUNE6, NATHALIE TESTARD6, PIERRE PETERLIN7, PATRICE CHEVALLIER7, LUCIENNE CHATENOUD8, JEAN-HUGUES DALLE9,

MAXIME CRAVAT1, MÉLANIE GAUTHIER1,3, VÉRONIQUE DECOT1,3, LOIC REPPEL1,3, DANIÈLE BENSOUSSAN1,3 1CHRU DE NANCY, HÔPITAL BRABOIS, NANCY, FRANCE, 2CHU DE TOULOUSE, HÔPITAL PURPAN, TOULOUSE,

FRANCE, 3UMR 7635 CNRS-UNIVERSITÉ DE LORRAINE, INGÉNIERIE MOLÉCULAIRE ET PHYSIOPATHOLOGIE ARTICULAIRE (IMOPA), CAMPUS BIOLOGIE-SANTÉ, NANCY, FRANCE, 4CHU DE MONTPELLIER, MONTPELLIER, FRANCE,

5LAUSANNE UNIVERSITY HOSPITAL, LAUSANNE, SWITZERLAND, 6CHD DE VENDÉE, LA ROCHE-SUR-YON, FRANCE, 7CHU DE NANTES, HÔTEL-DIEU, NANTES, FRANCE, 8AP-HP, HÔPITAL NECKER, PARIS, FRANCE, 9AP-HP,

HÔPITAL ROBERT DEBRÉ, HEAD OF THE FRENCH ATMP GROUP, UNDER THE AEGES OF SFGM-TC, PARIS, FRANCE BACKGROUND: Adoptive transfer of polyomavirus-specific T lymphocytes (VST-PyV) is a highly

promising therapy for accelerating immune reconstitution in patients, thereby reducing the occurrence or severity of deadly viral diseases (JC virus-induced progressive multifocal

leukoencephalopathy (PML) and BK virus-induced hemorrhagic cystitis (HC)) during the period of immunodepression. METHODS: The VST-PyV was generated after collecting a leukapheresis from a

haploidentical donor displaying a cellular anti-PyV immune response. An immunomagnetic isolation of IFN-γ secreting cells after stimulation by peptide pools covering the entire

immunodominant proteins of PyV (VP1 and LT) was performed on the Prodigy device (Miltenyi Biotec, Germany). This method was carried out at the ATMP Department of the Nancy University

Hospital, where cells were produced under Good Manufacturing Practices (GMP) grade conditions before infusion. Part of the leukapheresis was frozen to perform other immunomagnetic isolations

for the same patient in order to reach 2 to 3 infusions one month apart. RESULTS: Infusions were carried out in 4 patients suffering from polyomavirus infections. Three patients had proven

virological PML, among which 2 developed the PML after having received an allogeneic hematopoietic stem cell transplantation (HSCT) with a matched unrelated donor or a haploidentical donor

for a malignant hematological disease. The third PML patient received a bi-pulmonary transplant. Immunosuppressive therapies were reduced or stopped after PML diagnosis, with no effect on

disease progression. The fourth patient developed an HC following a haploidentical HSCT for acute myeloblastic leukemia, which failed to resolve despite infusions of polyvalent

immunoglobulins and Cidofovir (2 infusions). For the 3 PML patients, 2 ± 1 VST-PyV infusions were performed with an average of 0.399x106 live mononuclear cells containing 0.187x104 CD3+/Kg

and 0.139x104 CD3+IFN-γ+/Kg. One HSCT patient died from PML 27 days after having received a unique infusion. In the other two patients, follow-up showed control of JC virus replication in

the cerebrospinal fluid preceding clinical improvement with various degrees of neurological sequelae. In the case of the HC patient, a single infusion of VST-PyV (CD3+ = 1.05 x 104/Kg,

CD3+IFN-γ+ = 0.692 x 104/Kg) was associated with the demonstration of a significant specific immune response, BK virus clearance, and a favorable outcome of the cystitis. The infusions were

well tolerated by the four patients, with no adverse effects, including Graft versus Host Disease (GvHD). CONCLUSIONS: Diseases related to PyV infections are rare but often disabling or

fatal post-transplant complications for which few therapeutic options are available. VST-PyV is a safe therapeutic option with promising efficacy that should be implemented as soon as

possible in the course of the opportunistic infection. DISCLOSURE: Nothing to declare. 36: PHARMACOLOGY P763 GANCICLOVIR THERAPEUTIC DRUG MONITORING FOR THE PREVENTION AND TREATMENT OF

CYTOMEGALOVIRUS IN IMMUNOCOMPROMISED CHILDREN HEATHER WEERDENBURG1,2,3, AMANDA GWEE1,2,3 1ROYAL CHILDREN’S HOSPITAL, MELBOURNE, VIC, AUSTRALIA, 2MURDOCH CHILDREN’S RESEARCH INSTITUTE,

MELBOURNE, VIC, AUSTRALIA, 3THE UNIVERSITY OF MELBOURNE, MELBOURNE, VIC, AUSTRALIA BACKGROUND: Cytomegalovirus (CMV) infections in immunocompromised children impact treatment outcomes with

risks of treatment failure, and mortality. A ganciclovir area under the concentration-time curve (AUC24) of 40–60 mg.h/L is associated with successful prevention of CMV infection. We

evaluated the ganciclovir AUC24 in immunocompromised children receiving ganciclovir. METHODS: Retrospective audit over a 12-month period (2022–2023) of children aged <18 years with CMV

viraemia in who had ganciclovir monitoring. All children received ganciclovir 5 mg/kg 12 hourly and the AUC24 was calculated using web app with an embedded pharmacokinetic model. Children

received 5 mg/kg doses 12 hourly were used, with blood samples collected ≥48 hours post-initiation. RESULTS: Nineteen children (median age 9 years, range 0–17) including 9/19 stem cell

transplant recipients, 6/19 with malignancy, 4/19 with gastrointestinal conditions had ganciclovir AUC24 monitoring. The median AUC24 was 42 mg.h/L (range 25–67), with only 47% (9/19)

achieving an AUC24 ≥ 40 mg.h/L and 11% (2/19) an AUC24 ≥ 60 mg.h/L. A similar ganciclovir AUC24 was observed in stem cell transplant recipients (38 mg.h/L, range 25–63) to those with other

underlying diagnoses (43 mg.h/L, range 26–67). Adverse effects were reported in 7/19 (37%) children, with no clear correlation with AUC24: neutropenia occurred in 6/7 children with a median

AUC24 of 40 mg.h/L (range 25–63). Renal impairment occurred only in the two children who were receiving combination therapy with foscarnet (ganciclovir AUC24 35 and 55 mg.h/L). CONCLUSIONS:

Our study demonstrates low serum ganciclovir exposure in immunocompromised children. The wide AUC24 variability emphasises dosing complexities advocating for TDM and the need to explore the

relationship between AUC24 and clinical outcomes in this vulnerable cohort. CLINICAL TRIAL REGISTRY: NA. DISCLOSURE: Nothing to declare. 36: PHARMACOLOGY P764 NEW IN VITRO MODEL FOR

INVESTIGATING THE EFFECT OF GENETIC POLYMORPHISMS ON _GSTA1_ PROMOTER ACTIVITY, ONE OF THE KEY DETERMINANTS OF BUSULFAN INTERINDIVIDUAL VARIABILITY YVONNE GLOOR1, VID MLAKAR1, KHALIL BEN

HASSINE1, ISABELLE DUPANLOUP1, MARC ANSARI1,2 1UNIVERSITY OF GENEVA, GENEVA, SWITZERLAND, 2GENEVA UNIVERSITY HOSPITALS, GENEVA, SWITZERLAND BACKGROUND: Busulfan (Bu) is commonly used in

conditioning regimens prior to hematopoietic stem cell transplantation and the extent of Bu exposure is known to significantly impact treatment outcome in pediatric patients. Bu is mainly

metabolized by GSTA1 in the liver. We have previously shown that six single nucleotide polymorphisms (SNPs) located in the promoter region of _GSTA1_ influence gene expression in vitro and

the corresponding diplotypes correlate with Bu clearance in children [1–3]. However, the initial in vitro characterization of _GSTA1_ promoter polymorphisms was performed in a cell line with

limited metabolic capacities potentially impacting the relevance of those findings and hampering further investigation. To confirm our previous observations and investigate the mechanisms

regulating _GSTA1_ expression that contribute to interindividual variability, we replicated this experiment in a different hepatic cell line with more physiological liver functions. [1]

Mlakar et al. Sci Rep. 2021 [2] Ansari et al. Oncotarget. 2017 [3] Ben Hassine et al. CPT Pharmacometrics Syst Pharmacol.2021 METHODS: The _GSTA1_ promoter activity experiments performed

initially in HepG2 were reproduced in HepaRG cells. The Dual-Luciferase® reporter assay (pGL4, Promega) was used to measure reporter gene expression driven by 17 different _GSTA1_ promoters

composed of different combinations of the 6 SNPs known to affect promoter activity. The constructs were designed to represent all _GSTA1_ promoter haplotypes observed in humans and some

additional informative hypothetic variants. The assay was performed 24h post-transfection and luminescence measured on a Tecan Infinite® MPlex. Baseline luciferase activity was determined

from a promoter-less construct, also used for normalization. RESULTS: All _GSTA1_ promoter variants had a significant effect on luciferase gene expression in HepaRG cells. Indeed, even the

constructs with lowest activity showed a two-fold increase over the background fluorescence measured from the promoter-less variant, while 6 of those constructs were silent in HepG2 cells.

Similarly, the activity of the _GSTA1_ promoter reference haplotype (*A1) was nearly four-fold higher in HepaRG than in HepG2. _GSTA1_ promoters are commonly classified in two categories

correlating with promoter activity (*A > *B). This difference in expression is readily captured in HepaRG cells with strict segregation of the two promoter categories and a marked

increase from one category to the next, while in HepG2 cells differences in reporter expression levels followed a continuum with some category overlaps. CONCLUSIONS: We established a

reliable working model for the study of the _GSTA1_ promoter polymorphisms in vitro. Our observations are in line with previous knowledge reporting higher _GSTA1_ expression levels in HepaRG

than HepG2 cells. More importantly, we confirm differences in activity level between the promoter variants. Thus, our new model will enable us to further investigate the transcriptional

regulation of _GSTA1_ gene expression. CLINICAL TRIAL REGISTRY: NA. DISCLOSURE: Nothing to declare. 36: PHARMACOLOGY P765 DOSE MODIFICATIONS OF FLUDARABINE AS PART OF FLUDARABINE AND

CYCLOPHOSPHAMIDE (FC) LYMPHODEPLETION IN PATIENTS WITH RENAL IMPAIRMENT RECEIVING LICENSED CAR-T CELL THERAPIES IN THE UK JACKIE CHAPPELL1, NIA EVANS2, RACHEL PALMER3, SUMANTHA GABRIEL4,

JESSICA PEALING5, ELIZABETH DAVIES6, AMRIT ATWAL7, JENNIFER PIRRIE8, SOKAR LEGARD9, VICTORIA POTTER1, ROBIN SANDERSON1 1KING’S COLLEGE HOSPITAL NHS FOUNDATION TRUST, LONDON, UK, 2UNIVERSITY

HOSPITAL OF WALES, CARDIFF, UK, 3UNIVERSITY HOSPITALS BRISTOL AND WESTON NHS FOUNDATION TRUST, BRISTOL, UK, 4THE NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST, NEWCASTLE UPON TYNE, UK,

5THE CHRISTIE HOSPITAL, MANCHESTER, UK, 6MANCHESTER UNIVERSITY NHS FOUNDATION TRUST, MANCHESTER, UK, 7UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST, BIRMINGHAM, UK, 8THE QUEEN

ELIZABETH UNIVERSITY HOSPITAL, GLASGOW, UK, 9THE LEEDS TEACHING HOSPITALS NHS TRUST, LEEDS, UK BACKGROUND: The recommended lymphodepletion regimens for the three chimeric antigen receptor

T-cell (CAR-T) therapies licensed in the UK (Yescarta®, Kymriah® and Tecartus®) consist of fludarabine and cyclophosphamide (FC). There are no specific recommendations in the CAR-T Summary

of Product Characteristics (SmPCs) for dose adjustments of these two drugs for patients with renal impairment. A survey of UK CAR-T centres by the Clinical and Educational subgroup of the

Pan UK ATMP (Advanced Therapy Medicinal Product) Pharmacy Working Group indicated that practice across the UK is variable and there is presently no consensus on dose amendments in renal

impairment for fludarabine administered as part of FC lymphodepletion. The fludarabine UK SmPC recommends a fludarabine dose reduction for patients with a creatinine clearance (CrCL) ≤70

ml/min however the evidence for this reduction remains unclear in this setting. The aim of this project was to establish the variation in fludarabine dose administered as part of FC

lymphodepletion across UK CAR-T centres. METHODS: Anonymised patient data was collected retrospectively for all adult patients treated in participating UK CAR-T centres with licensed CAR-T

therapies between January 2019 and May 2021 to ascertain current practice for fludarabine dose adjustments in this setting. Data collected included: Patient demographics; CAR-T product;

indication; number of patients treated with normal renal function vs renal impairment (CrCL ≤70 ml/min); method of measuring renal function; fludarabine doses administered (percentage (%) of

SmPC recommended dose in normal renal function); rates of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). RESULTS: We collected data from

nine UK CAR-T centres for 321 patients (125 female, 196 male; age range 18 to 81 years). 229 patients received Yescarta®, 87 Kymriah® and 5 Tecartus®. 76 (23.6%) patients had a documented

CrCL ≤70 ml/min. Three different methods were used to measure renal function: EDTA CrCL 85 (26.5%) patients, 24-hour urine collection 86 (26.8%) patients and Cockroft & Gault equation

CrCL 150 (46.7%) patients. Table 1 illustrates the range of fludarabine dosing according to CrCL and patient age. TABLE 1: PATIENTS WITH RENAL IMPAIRMENT (CRCL ≤70 ML/MIN): FLUDARABINE DOSES

ADMINISTERED (EXPRESSED AS % OF SMPC RECOMMENDED DOSE IN NORMAL RENAL FUNCTION) Overall rates of CRS ≥ Grades 3-4 and ICANS ≥ Grades 3-4 for all patients who received 100% fludarabine dose

were 11.6% (32 patients) and 12.3% (34 patients) respectively compared with patients with CrCL ≤70ml/min receiving 100% fludarabine dose 11.8% (4 patients) and 11.8% (4 patients) and

patients with CrCL ≤70 ml/min receiving reduced fludarabine doses 4.8% (2 patients) and 11.9% (5 patients). CONCLUSIONS: We identified six different strategies for dosing fludarabine in

renal impairment in FC lymphodepletion in use across the UK and have documented the variation of doses of fludarabine as part of FC lymphodepletion in our patient dataset and relative rates

of CRS and ICANS. We now plan to identify any further variations in toxicities and patient outcomes between the patient groups studied with an aim to develop some national consensus

guidelines for dosing fludarabine in renal impairment in FC lymphodepletion. CLINICAL TRIAL REGISTRY: N/A. DISCLOSURE: Jackie Chappell - Nothing to declare. Robin Sanderson - Honoraria and

travel expenses from Kite Gilead. Victoria Potter - Nothing to declare. Nia Evans - Nothing to declare. Rachel Palmer - Nothing to declare. Sumantha Gabriel - Nothing to declare. Jessica

Pealing - Nothing to declare. Elizabeth Davies - Nothing to declare. Amrit Atwal - Nothing to declare. Jennifer Pirrie - Nothing to declare. Sokar Legard - Nothing to declare. 36:

PHARMACOLOGY P766 PAEDI VOD INSIGHTS: REVIEWING VENO-OCCLUSIVE DISEASE IN PAEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTS – INCIDENCE, RISK FACTORS, AND ANTIFUNGAL IMPACT HEATHER

WEERDENBURG1,2,3, HANNAH WALKER1,2,3 1ROYAL CHILDREN’S HOSPITAL, MELBOURNE, VIC, AUSTRALIA, 2MURDOCH CHILDREN’S RESEARCH INSTITUTE, MELBOURNE, VIC, AUSTRALIA, 3THE UNIVERSITY OF MELBOURNE,

MELBOURNE, VIC, AUSTRALIA BACKGROUND: Paediatric allogeneic haematopoietic stem cell transplant (HCT) recipients are at risk of veno-occlusive disease (VOD) with multiple factors

contributing including antifungals. METHODS: A single-centre retrospective analysis was conducted at The Royal Children’s Hospital, Melbourne, Australia, to investigate the incidence of VOD

in paediatric allogeneic hematopoietic stem cell transplant (HSCT) recipients. Clinical and patient demographic data, including pre-transplant regimens, conditioning regimen and supportive

care details were extracted from medical records. VOD specific risk factors, such as conditioning regimens and patient characteristics, were reviewed based on the European Society for Blood

and Marrow Transplantation (EBMT) guidelines.1 Descriptive statistics, including frequencies and percentages, were employed to characterize the cohort. Chi-square tests and t-tests were used

to assess associations and differences between groups, respectively. The significance level was set at a _p_ value < 0.05. RESULTS: There were 203 patients (median age: 6.9 years, IQR:

3.1 to 13.0) with 222 episodes of allogenic HCT captured from 2016–2022. One-hundred and eighty-four children received a single transplant, 19 received multiple HCT. Indication for HCT was

either malignant (132/222, 59.5%) or non-malignant conditions (90/222, 40.5%). Type of donor and conditioning regimen along with patient characteristics are mentioned in table 1. Overall

incidence of VOD was 16.7% (34/203). Four children (4/34, _p_ = 0.45) were diagnosed with VOD post a second HCT. The median age of HCT on day 0 in children diagnosed with VOD was younger;

median 3.9 years (IQR: 1.2–10.0) compared to the non-VOD cohort; median 7.9 years (IQR: 3.7–13.5). Younger age is a defined risk factor for VOD and was significant in this cohort (_p_ < 

0.05), particularly children under 2 years old who constituted 33% (11/34, _p_ < 0.05) of the instances of VOD potentially associated with immature liver development. Use of busulfan

(42.3%, 94/222), and in combination with cyclophosphamide (4.5%, 10/222) were significant risk factors, there were low numbers with other agents. Previous immunotherapy (blinatumomab and

inotuzumab), and specific childhood diseases, such as infantile osteopetrosis, and JMML had a proportion in the VOD group. Despite these associations, statistical analyses revealed no

significant difference in VOD incidences. Choice of antifungal during conditioning until day +30 is a recognised hepatic risk factor, in our cohort fluconazole (182/250 incidences) followed

by voriconazole (35/250) was the most administered antifungal. There was varying associations with VOD however differences observed were not statistically significant. Table 1: Detailed

patient characteristics References 1. Corbacioglu S, Carreras E, Ansari M, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric

patients: a new classification from the European society for blood and marrow transplantation. _Bone Marrow Transplant_. 2018;53(2):138–145. CONCLUSIONS: Our study reveals a VOD incidence of

16.7% showcasing potential variations in risk factors and treatment practices. Younger age, particularly <2 years and use of busulfan play a discernible role, warranting cautious

consideration in clinical decision making. While certain factors present discernible risks, the absence of statistical significance in-particular with antifungal choice signals a need for

further exploration. CLINICAL TRIAL REGISTRY: NA. DISCLOSURE: Nothing to declare. 36: PHARMACOLOGY P767 AN INVESTIGATION OF ANTIBIOTIC PROPHYLAXIS TO PREVENT PNEUMOCOCCAL INFECTION AFTER

STEM CELL TRANSPLANTATION ADAOLISA ANUNWA1, LAURA HAZLETT2, NICK DUNCAN 1,2 1UNIVERSITY OF BIRMINGHAM, BIRMINGHAM, UK, 2QUEEN ELIZABETH HOSPITAL, BIRMINGHAM, UK BACKGROUND: Hyposplenia after

stem cell transplantation (SCT), increases the risk of infection with encapsulated bacteria, particularly _Streptococcus pneumoniae_. Infections can be life-threatening and prophylactic

measures, including long-term antibiotic prophylaxis, are widely recommended for at-risk patients. The aims of this study were to determine current practice in relation to anti-pneumococcal

antibiotic prophylaxis in transplant centres in the United Kingdom (UK) and Republic of Ireland (ROI) and to investigate levels of adherence to prophylaxis in allograft recipients. METHODS:

An electronic survey of practice was designed (using the www.onlinesurveys.ac.uk platform) and sent to all adult allograft centres (_n_ = 25) in the UK and ROI via the UK BMT Pharmacists

Group. The survey was open October-November 2023. All responses were collated and analysed using Microsoft Excel®. Additionally, all allograft patients attending the late effects clinic at

the Queen Elizabeth Hospital, Birmingham over a similar time period were asked about their adherence behaviours in relation to prophylactic anti-pneumococcal antibiotics. RESULTS: Responses

were received from 25 centres. 22/25 centres (88%) routinely prescribed anti-pneumococcal prophylaxis to allograft patients post-transplant. 8/25 (32%) also prescribed it to autograft

recipients. Penicillin VK 250 mg bd was the most widely used agent and schedule (18 centres). Alternatives were penicillin VK 500 mg bd (two centres), amoxicillin 500 mg od (one centre) and

co-trimoxazole (one centre). Macrolides [erythromycin (250–500 mg bd) or clarithromycin (250 mg od-bd) were the most widely prescribed drugs in cases of penicillin allergy. Three centres

used ciprofloxacin in this setting and one used cephalexin. Of the 22 centres routinely prescribing prophylaxis, 12 (55%) recommended lifelong prophylaxis for all allograft recipients. The

remaining 10 centres deviated from this in terms of different approaches for specific sub-groups of patients (e.g. only TBI recipients receiving prophylaxis) and/or different durations of

prophylaxis (e.g. stopping after five years). Adherence data were collected from 55 patients (32 male, 24 female). Median age was 58 (range 23–83). The median time since transplant was 9

years (range 2–37). 7/55 patients (13%) had stopped taking antibiotic prophylaxis (hospital policy recommends lifelong prophylaxis). 22% of males had stopped prophylaxis vs 0% of females

(_p_ = 0.016%, Fishers’ exact test). 31/48 patients (65%) who were still taking prophylaxis reported 100% adherence to their antibiotic schedule. Female patients were more likely to be fully

adherent then male patients (83% vs. 48%, _p_ = 0.012), and there was also an association between current age and adherence. No other factor was found to significantly impact on adherence

behaviours – see table. Factor Category Adherent (_n_ = 31) Non-adherent (_n_ = 17) _P_-value Gender Male (_n_ = 25) 12 (48%) 13 (52%) 0.012 (CHI-SQUARED TEST) Female (_n_ = 23) 19 (83%) 4

(17%) Conditioning Reduced intensity (_n_ = 25) 18 (72%) 7 (28%) 0.262 (Chi-squared test) Myeloablative (_n_ = 23) 13 (57%) 10 (43%) Time since transplant ≤10 years (_n_ = 26) 17 (65%) 9

(35%) 0.900 (Chi-squared test) >10 years (_n_ = 22) 14 (64%) 8 (36%) Age at last follow-up (median)   65 (range 24–83) 50 (range 23–68) 0.002 (MANN-WHITNEY U-TEST) CONCLUSIONS: This is

the first comprehensive survey (100% response rate) of anti-pneumococcal antibiotic practice within the UK/ROI SCT setting. Antibiotic prophylaxis was not universally prescribed and in those

centres who did employ routine prophylaxis, marked variability was observed, particularly in relation to eligible populations and antibiotic duration. Updated guidance at a country or EBMT

level may be required to help standardise practice. In relation to patient behaviour at a single hospital, this study has demonstrated high levels of persistence with a lifelong prophylaxis

schedule. Younger age and male gender appear to predict for suboptimal adherence and such groups may benefit from enhanced health care professional support. DISCLOSURE: Nothing to declare.

36: PHARMACOLOGY P768 MOCRAVIMOD DOES NOT HAVE A CLINICALLY RELEVANT DRUG-DRUG INTERACTION WITH STRONG CYP3A4 INHIBITOR ITRACONAZOLE DYMPHY HUNTJENS1, STEPHAN OEHEN1, ELISABETH KUEENBURG1

1PRIOTHERA SAS, SAINT-LOUIS, FRANCE BACKGROUND: Mocravimod (MOC), a novel sphingosine-1-phosphate receptor (S1PR) functional antagonist in phase 3 development in patients with acute myeloid

leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (allo-HCT), is predominantly metabolized via the CYP3A4 pathway based upon in vitro data. Preliminary data on

pharmacokinetic (PK) modeling of phase 1b data suggested that CYP3A4 inhibitors, could potentially increase exposure to MOC significantly. Given the need for co-administration of MOC with

CYP3A4 inhibitors such as azoles in allo-HCT patients, a dedicated phase 1 study was conducted to evaluate the drug-drug interaction (DDI) of MOC in combination with itraconazole (ITZ).

METHODS: A phase 1, open-label fixed sequence study was conducted in healthy volunteers (HV; _n_ = 19) to assess the effect of ITZ on a single dose MOC exposure. The study consisted of 2

treatment periods and a washout period of at least 4 weeks. In period 1, HV received a 3-mg MOC dose in the morning of Day 1 after a standard breakfast. In period 2, a daily dose of 200 mg

ITZ after a standard breakfast was given until Day 13. On day 5, the HV received a standard breakfast, their daily ITZ dose, followed by a 3-mg MOC dose 60 minutes after the ITZ dose. In

both periods, venous blood samples were collected over 360 hours after MOC administration for the determination of MOC and its active metabolite mocravimod-phosphate (MOC-P) in whole blood.

MOC and MOC-P have long half-lives of ~110 hours and therefore AUC0-inf was determined using non-linear mixed effect modeling. Ratios of geometric least square (LS) means and 90% CIs were

constructed for AUC0-inf and Cmax comparing periods 1 and 2. In addition, the safety and tolerability were monitored. RESULTS: ITZ co-administration with MOC did not affect the MOC and MOC-P

Cmax; geometric mean ratio (GMR) of 0.92 [0.85–1.01] and 0.99 [0.92-1.08] fold, respectively. AUC0-inf was similar and independent of ITZ co-administration; GMR of 1.04 [0.97–1.11] and 1.11

[1.04–1.18] for MOC and MOC-P, respectively. Based on the mechanism of action of S1PR modulators bradycardia is a potential adverse event (AE) class effect and the pharmacodynamic effect

resulting in the therapeutic effects is the prevention of lymphocyte egress from lymphoid tissue to the circulation, resulting in lymphopenia and thus reduced homing to susceptible target

organs such as the gut, skin, or the central nervous system (CNS). In this study, bradycardia (88% of HV in part 1 and 84% in part 2) and lymphocyte count decreases (76% of HV in part 1 and

68% in part 2) were the most common AEs. AEs were generally mild, and treatment emergent AEs were similar in period 1 and period 2, indicating limited effect of combination treatment.

CONCLUSIONS: MOC and ITZ were generally well tolerated when administered alone or in combination. The PK of MOC and MOC-P are bioequivalent with or without co-administration of multiple

doses of the strong CYP3A4 inhibitor ITZ. Taken together, MOC can be co-administered with CYP3A4 inhibitors such as azoles without dosage adjustments in allo-HCT patients. DISCLOSURE: Dymphy

Huntjens is an employee of Priothera SAS. Stephan Oehen is an employee of Priothera SAS. Elisabeth Kueenburg is an employee of Priothera SAS. 36: PHARMACOLOGY P769 DO WEIGHT-BASED DOSE

MODIFICATIONS IMPACT THE SEVERITY OF MUCOSITIS IN ADULT PATIENTS RECEIVING BUSULFAN AS PART OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT CONDITIONING? KATHERINE CUTHBERT1, SINEAD

CONNOLLY1 1SCOTTISH NATIONAL CENTRE FOR ADULT ALLOGENEIC STEM CELL TRANSPLANT/CAR-T THERAPY, GLASGOW, UK BACKGROUND: Busulfan is an alkylating agent frequently used as part of conditioning

regimens for hematopoietic allogenic stem cell transplantation (HSCT), and has a narrow therapeutic index. Mucositis is one of the most debilitating adverse events in patients undergoing

HSCT1 and is a documented side effect of busulfan therapy2. Moreover, mucositis is a critical risk factor for infections3 and data supports increased risk of severe mucositis using

myeloablative (MA) rather than reduced intensity (RIC) conditioning regimens4. An ASBMT position statement is available5, which recommends using adjusted ideal body weight (AIBW) for all

busulfan dosing whereas the SPC for busulfan only recommends dose adjustments if BMI > 302. There remains variation in weight-based dose modifications across UK Centres. The severity of

mucositis for all patients receiving busulfan-based HSCT conditioning (MA or RIC) at the Scottish National Adult Allogeneic Stem Cell Transplant Unit in a 1 year period was audited along

with any dose-based modifications to try to elicit if dose modifications impact mucositis severity. METHODS: A retrospective review of all patients (26) who received busulfan for HSCT at

this centre between November 2022–2023. Data collected included busulfan dose (ABW V AIBW), regimen (MA v RIC), and severity of mucositis. This was retrospectively reviewed to confirm if

busulfan was dose adjusted as per SPC2 and to record whether the regimen was MA or RIC, along with the severity of mucositis recorded during the acute transplant period using the common

terminology criteria for adverse events (CTCAE). The association between busulfan dose or regimen and severity of mucositis was tested using Fisher’s exact test. RESULTS: 100% of patients

developed mucositis (Table 1). 16/26 (62%) patients received MA conditioning. 12/16 (75%) of patients who received MA conditioning experienced severe (≥grade 3) mucositis, whilst only 1/10

(10%) patients who received RIC had severe mucositis; showing a significant difference in the severity of mucositis between the two types of conditioning regimens (_p_ value = 

0.004).12/26(47%) received dose adjusted busulfan. Within the MA conditioning group, 5/16 (31%) received dose adjusted busulfan and still recorded severe mucositis. This was not deemed

significantly less than the 7/16 (44%) who recorded severe mucositis without dose modification (_p_ value = 1). 8/10 (80%) patients who received RIC conditioning scored grade 1 mucositis, of

which 50% received dose adjusted busulfan; showing no significance in mucositis for weight adjusted dosing (_p_ value = 1). CONCLUSIONS: In conclusion, there was no increased incidence of

severe (≥Grade 3) mucositis in the actual body weight group in both MA and RIC transplants. However, results did show a significant difference between the two conditioning regimens, with MA

conditioning having a significantly increased incidence of severe mucositis compared to RIC. Advanced age, medical co-morbidities, and prior therapy can preclude the use of MA conditioning;

these may also be confounding factors for the development of mucositis. Patient numbers in this study are too small to allow for an adjusted analysis accounting for confounding factors but

this could be further investigated in the future as more data are available. DISCLOSURE: Nothing to declare. 36: PHARMACOLOGY P770 DOES PROCALCITONIN ACCURATELY DIFFERENTIATE BETWEEN CRS AND

BACTERIAL SEPSIS IN CAR-T PATIENTS? DOES PROCALCITONIN ACCURATELY DIFFERENTIATE BETWEEN CRS AND BACTERIAL SEPSIS IN CAR-T PATIENTS? DOUGLAS SEMPLE1, SINEAD CONNOLLY2 1BEATSON WEST OF

SCOTLAND CANCER CENTRE, GLASGOW, UK, 2QUEEN ELIZABETH UNIVERSITY HOSPITAL, GLASGOW, UK BACKGROUND: Since January 2020, 103 adult patients received CAR-T therapy at the Scottish National

CAR-T Centre, Glasgow. Accurately differentiating between cytokine release syndrome (CRS) and bacterial sepsis is challenging in this patient cohort. Procalcitonin is an acute phase reactant

which has been shown to be a sensitive marker in patients with bacterial sepsis differentiating this from other types of inflammation such as cytokine release syndrome (CRS)1. Recent

research shows an association between raised procalcitonin levels and bacterial sepsis in CAR-T patients1,2. Procalcitonin is used ad-hoc at present in this centre to help guide treatment in

patients post CAR-T infusion who develop symptoms of CRS. This retrospective study aimed to determine if raised procalcitonin was predictive of bacterial sepsis in our local population.

METHODS: Retrospective case note review of all patients who received CAR-T therapy in Scotland since January 2020. Locally, a procalcitonin level <0.5 ng/ml is regarded as a low risk of

severe sepsis with a level >2ng/ml as high risk of severe sepsis. These cut-offs are different from the values used in recent research2. Procalcitonin levels (low risk, high risk, and

intermediate risk) were compared with corresponding blood cultures to determine if there was evidence of bacterial sepsis. CRP and antibiotic use at the time of the level was also recorded,

if available. RESULTS: 11/103 (11%) CAR-T patients had procalcitonin levels measured. Of those, 10 were reported and only one of these levels was high at 2.87 ng/ml. Blood cultures on the

day of the level, the day before, and the day after showed no evidence of bacteraemia despite the high procalcitonin level. In another instance, a low level of 0.18 ng/ml was observed on the

same day peripheral blood was cultured for both Staphylococcus epidermidis and Staphylococcus hominis. This patient received concurrent antibiotic treatment from two days before until two

weeks after this level. In one other patient, a low level of 0.24 ng/ml was observed two days after three species of staphylococcus were detected in peripheral blood. No growth was however

detected the day prior to the level. This patient was also on concurrent antibiotic treatment with meropenem throughout this time. In all other cases, observed low levels were associated

with no growth of bacteria in peripheral blood. CONCLUSIONS: Data collection has shown a lack of correlation between procalcitonin levels and accurate prediction of bacterial sepsis. This is

not in line with research2 but could be explained in part with data at present being limited. Further work will be required to accurately determine the place of procalcitonin in determining

the cause of SIRS in CAR-T patients. This data set combined with the recent research could be used as the basis for a prospective multi-centre study to evaluate this question further. * 1.

Rajeski K et al. Identifying Early infection in the setting of CRS with routine and exploratory serum proteomics and the HT10 score following CD19 CAR-T for relapsed/refractory B-NHL.

European Haematology association. * 2. Powell MZ et al. Procalcitonin as a biomarkers for predicting bacterial infection in chimeric antigen receptor T-cell therapy recipients. _Cancer

Medicine_ 2023. 12:9228-9235 DISCLOSURE: NA. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE The 50th Annual Meeting of the European Society for Blood

and Marrow Transplantation: Pharmacist Committee – Poster Session (P762-P770). _Bone Marrow Transplant_ 59 (Suppl 1), 735–742 (2024). https://doi.org/10.1038/s41409-024-02353-9 Download

citation * Published: 08 October 2024 * Issue Date: October 2024 * DOI: https://doi.org/10.1038/s41409-024-02353-9 SHARE THIS ARTICLE Anyone you share the following link with will be able to

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