Conference Fees Research Articles

P081 Out-patient management of gout in secondary care: Results from the North West regional audit

Abstract Background/Aims Recommendations for gout management have significantly evolved as outlined by the latest National Institute for Health and Care Excellence (NICE), European League Against Rheumatism (EULAR), British Society for Rheumatology (BSR) and the Medicines and Healthcare products Regulatory Agency (MHRA) guidelines, with increased emphasis being placed on optimising cardiovascular risk. This regional audit aimed to assess concordance with these guidelines within rheumatology outpatient settings in the North West region of England. Methods New or follow-up patients with gout, presenting to a rheumatology outpatient setting within the Greater Manchester and Lancashire area over a five-week period between 1/3/23 and 7/4/23 were included. We collated data on demographics, co-morbidity assessment including cardiovascular risk, prescribing of febuxostat in major cardiovascular disease, diuretic use and advice, setting of treat-to-target levels, use of cardiovascular risk prediction tools and subsequent follow up arrangements. For new patients, collected data also included referral reason, and prescription recommendations for first-line urate-lowering therapy (ULT) and co-prescriptions for flare prophylaxis. Results Ninety-two patients (mean age 60 years, 80% male) were included from 13 rheumatology departments. Twenty-three patients were new referrals. Sixty-seven patients (73%) had ≥ 1 relevant comorbidity; hypertension being the most common (55%). Twenty (22%) patients were on diuretics. Twelve (55%) of these patients had a diagnosis of hypertension without heart failure; none received recommendations to reduce or stop diuretics. In line with current guidelines, no patient with major cardiovascular disease was treated with febuxostat. Treat-to-target levels were agreed in 49 (57%) applicable patients. Cardiovascular prediction tools were only calculated or known in three (3%) patients. However, clinic data collected would have allowed a risk assessment calculation in 13 (14%) patients. Sixteen (17%) patients audited had no planned follow-up. Compared to NICE guidelines, 18 (78%) new patients reviewed in clinic were referred appropriately to rheumatology services. Twenty-two (96%) new patients referred were eligible to start ULT, of which 15 (75%) were started on a NICE/ EULAR recommended first-line ULT treatment (14 patients on allopurinol including 11 patients with no major cardiovascular disease, one patient on febuxostat). Eleven (79%) patients started on allopurinol were initiated on a low dose (50-100mg), as recommended by NICE and the BSR. Ten (67%) patients of those initiated on ULT were also prescribed prophylactic colchicine. Two additional patients were prescribed NSAIDs with PPI cover and one patient was prescribed oral steroids without PPI cover. Conclusion Most new patients were referred and prescribed first-line ULT treatment appropriately, often with colchicine prophylaxis. Uptake of febuxostat as first-line therapy was limited. Cardiovascular risk assessment was rarely done; further work exploring barriers to undertaking these assessments in rheumatology clinics is likely to improve both patient care and guideline compliance. Disclosure L. Gould: Other; L.G. has received conference fees from Eli Lilly. A. Richards: None. L. Gray: Other; L.G. has received travel and conference fees from Eli Lilly. M. Badarulla: Other; M.B. has received conference fees from Eli Lilly. L. Mercer: Other; L.M. has received conference fees from Nordic Pharma and UCB. R. Farid: None. R. Heaton: Consultancies; R.H. has received consultancy fees from Galapagos. Honoraria; R.H. has received speaker honorarium from Abbvie and Nordic. Other; R.H. has received conference fees from UCB. M. Al-Attar: None. M. Whitehead: None. S. Kamath: None. L. Teh: None. A. Odekunle: None. C.A. Sharp: None. A. Babiker: None. S. Hopping: None. A. Oldroyd: None. K. Lazarewicz: None. C. Saleh: None. S. Horton: None. D. Roy: Honoraria; D.R. has an honorary University of Manchester research assistant contract. A. Opeseyitan: None. D. Das: None. S. Varughese: None. D. Yidana: None. S. Wig: None. J. Bluett: Grants/research support; J.B. has received a research grant award from Pfizer. Other; J.B. has received travel/conference fees from UCB, Fresenius Kabi, Pfizer and Eli Lilly.

P118 Patient-reported outcomes, disease activity and safety in UK patients with rheumatoid arthritis treated with filgotinib: up to six-month interim results from a prospective observational study (FILOSOPHY)

Abstract Background/Aims FILOSOPHY (NCT04871919), an ongoing, observational Phase 4 study, will assess the effectiveness and safety of filgotinib, a JAK1-preferential inhibitor, in patients with RA in a real-world setting in Europe. We report interim UK data. Methods FILOSOPHY will enroll approximately 1,500 adults with moderate-to-severe active RA, upon first exposure to filgotinib, prescribed according to the product label and local standard-of-care. DAS28-CRP and CDAI were assessed at baseline, Month one, three and six and pain (visual analog scale [VAS]) and FACIT-Fatigue score at baseline, Week one, two and three and Month one, three and six. A reduction of ≥ 10 mm in VAS pain or increase of ≥ 4 in FACIT-Fatigue score were considered a clinically meaningful change from baseline (CFB). Treatment-emergent adverse events (TEAEs) on study were reported. Results By January 31, 2023, 130 patients had been treated in the UK; baseline characteristics and study treatment are reported in the Table. Median (IQR) CFB in DAS28-CRP was -1.1 (-2.5, -0.5) at Month one (N = 29), -1.7 (-2.6, -1.2) at Month 3 (N = 32) and -2.5 (-3.2, -1.0) at Month six (N = 27). Median (IQR) CFB in CDAI was -15.0 (-26.0, -8.0) at Month one (N = 31), -17.0 (-27.0, -12.0) at Month three (N = 31) and -25.0 (-30.0, -16.0) at Month 6 (N = 30). The proportion of patients with a clinically meaningful CFB in FACIT-Fatigue score was 45.0% (n = 18/40) at Week 1 and 65.6% (n = 21/32) at Month six. For VAS pain, the proportions were 47.5% (n = 19/40) at Week 1 and 66.7% (n = 22/33) at Month six. Similar trends were seen in the monotherapy and combination groups. No unexpected TEAEs occurred. Six patients discontinued the study prematurely; there was one death (lobar pneumonia); none were lost to follow-up. Conclusion Interim UK data showed pain and fatigue improved with filgotinib treatment as early as Week one and disease activity as early as Month one, the first timepoint that DAS28-CRP and CDAI were assessed; improvements were maintained up to Month six. While conclusions regarding safety cannot be made due to the short follow-up and small sample size, no new safety findings were observed. Long-term follow-up is needed to further evaluate effectiveness and safety. Disclosure B. Kirkham: Consultancies; AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, Novartis. N.D. McKay: Consultancies; Gilead, UCB. Member of speakers’ bureau; Galapagos. Other; Registration for conference fees from AbbVie, Novartis, UCB. His department has received grants and payments from a wide range of pharmaceutical companies for research and education. A.G. Pratt: Consultancies; Inflection Biosciences (paid to Newcastle University). Grants/research support; Galapagos, GSK, Pfizer (paid to Newcastle University). J. Barry: Other; Employee of Galapagos. O. Bouzid: Consultancies; Galapagos. T.P.A. Debray: Consultancies; Biogen, Daiichi Sankyo, Galapagos, Gilead. S. Bhat: None. L. Robertson: Other; Financial support for conference attendance from UCB. J. Galloway: Consultancies; AbbVie, Galapagos, Janssen, Lilly, Pfizer. Honoraria; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Grants/research support; AstraZeneca, Janssen, Pfizer.

Financial Barriers to Surgical Conferences: A Cross-Sectional Analysis of Registration Fees.

Scientific meetings provide much educational value to participants of all career stages. There is a paucity of literature surrounding the costs of attending scientific meetings and how this may affect participation, especially among trainees. The objective of this study is to assess the accessibility of surgical conferences for attendees by analyzing costs related to surgical society membership and conference registration. Societal membership and conference registration fee data were collected according to career stage (i.e., student, resident, fellow, and staff) for the fourteen surgical specialties recognized by the American College of Surgeons (ACS). Fees for participants from low- and middle-income countries (LMICs) and for virtual-only attendance options were also collected when available. Overall, we included data from 46 surgical societies (32 North American, 14 European or global). The median conference fees for students in the member and non-member categories were 191.55 USD (IQR 42.22-320.99) and 452.40 USD (IQR 294.06-555.00), respectively, representing a 136.2% price increase if not a member. Median conference fees for residents, fellows, and staff in the member category were 65.5%, 66.9%, and 230.9% greater than that for students, respectively. Median prices for residents, fellows, and staff in the non-member category were 49.9%, 54.9%, and 49.9% greater than that for member trainees of the same category, respectively. Our results highlight the substantial costs associated with attending surgical conferences, especially for trainees, representing a significant barrier to already financially burdened trainees, especially those from LMICs, smaller institutions, or less well-off backgrounds.

E081 Effectiveness of intravenous belimumab in patients with systemic lupus erythematosus at a UK tertiary referral centre

Abstract Background/Aims Belimumab was approved in the United Kingdom (UK) in 2016 as add-on therapy for patients with auto-antibody positive systemic lupus erythematosus (SLE) and high disease activity refractory to standard treatment. Data regarding the effectiveness of belimumab outside clinical trials has been published in worldwide SLE cohorts but not the UK. Here, we describe the efficacy of add-on belimumab therapy in SLE patients from a large London tertiary centre. Methods We performed a retrospective, intention-to-treat analysis of clinical and biochemical outcomes, at 6 and 12 months, post receipt of at least 1 infusion of belimumab in SLE patients attending Guy’s and St Thomas’ NHS Trust (April 2013-November 2021). Outcomes assessed included: the Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), anti-dsDNA ELISA titre, complement C3 and C4 titres, urine protein:creatinine ratio (uPCR) and daily prednisolone dose. Analyses performed using SPSS statistics 27. Results 63 patients (56 female [88.9%], median age 38 years, self-reported race/ ethnicity; 24 Black [38.1%], 24 White [38.1%], 13 Asian [20.6%]) with SLE as defined by the 1997 ACR criteria were included. An 8-point reduction in median SELENA-SLEDAI was evident at 6 months after commencing belimumab, which increased to 9 points at 12 months (n = 28, p < 0.001)(Table 1). Improvements in C3/ C4 titres were also observed at 6 months (0.13-point and 0.04-point increase in median C3/ C4 titres respectively, n = 45, p < 0.001). At 12 months, significant reductions in median anti-dsDNA titre (16.50-point reduction, n = 42, p < 0.001) and median daily prednisolone dose were evident (2.50mg reduction, n = 51, p < 0.001). No change in uPCR was noted (n = 23, p = 0.956). 40/47 (85%) patients with a SELENA-SLEDAI score recorded at 6 months achieved the National Institute for Health and Care Excellence (NICE) defined target for a >/= 4-point reduction in SELENA-SLEDAI. No significant associations between baseline demographic variables and SELENA-SLEDAI score at 6 months, or prednisolone dose at 12 months, were evident. Conclusion We observed a significant improvement in SLE disease activity as determined by SELENA-SLEDAI score measured at 6 and 12 months after starting belimumab, and a significant steroid-sparing effect at 12 months. These findings are similar to published worldwide data. Disclosure G. Mallett: None. C. Hession: None. M. Fernando: Other; MF has received speaker fees from GlaxoSmithKline (GSK) and Union Chimique Belge (UCB), as well as conference fees from GSK.

Medical conferences and medical practice

Medical conferences and medical practice

P138 Real-world incidence and management of hypocalcaemia after denosumab administration in patients with chronic kidney disease: a UK secondary-care based audit

Abstract Background/Aims Hypocalcaemia is a recognized complication of denosumab therapy in patients with renal impairment. Our local protocol states that patients with creatinine clearance (CrCl) <35ml/min should have blood tests for calcium and renal function weekly for 4 weeks after each denosumab injection. This audit aimed to assess whether such patients underwent appropriate blood monitoring, and to evaluate the incidence, severity and management of hypocalcaemia in this patient population. Methods Patients who commenced denosumab between 2011 and March 2020 were eligible for inclusion if they had CrCl <35ml/min. Data collection was undertaken through retrospective review of clinical records and pathology systems. Results 53 patients fitting the above criteria were identified. One further patient with eGFR 32ml/min was also included, giving 54 patients in total for analysis. The age range of the patients was 76-97, 9/54 (17%) were male. None were on renal replacement therapy. 29/52 patients (56%) missed one or more post-injection blood tests (incomplete data n = 2). The most commonly missed blood tests were the 1st and 4th weekly checks. 18/54 (33%) developed hypocalcaemia at some point after starting denosumab. In 8/18 this was a one-off episode, but 10/18 experienced recurrent hypocalcaemia. Lowest values for adjusted calcium varied from 1.83-2.18mmol/l. Only 3 patients had a value <2.0mmol/l. Patients who did and did not develop hypocalcaemia had a mean (SD) CrCl of 27.3 (5.03) and 27.8 (5.19) respectively. There was no significant difference in CrCl between these two groups (unpaired t-test, p value 0.7338). Comparing those with >1 episode of hypocalcaemia with the rest of the group, again the mean CrCl was not significantly different (26.6 vs. 27.9, p = 0.47). The three patients who developed more severe hypocalcaemia (adjusted calcium <2.00mmol/l) had CrCl values of 33.2, 24.0 and 21.0ml/min. 17/18 patients who developed hypocalcaemia were on combined calcium and vitamin D supplementation. One patient was on vitamin D3 alone due to intolerance of calcium supplements - they developed mild hypocalcaemia only (nadir 2.13mmol/l) and had CrCl 27ml/min. One patient with CrCl 21ml/min became hypercalcaemic on combined supplementation which was later switched to alfacalcidol by the renal team. Hypocalcaemia was most commonly observed 1-week post-injection, but delayed onset of hypocalcaemia 4-6 weeks post-injection was observed in a few cases. Most episodes resolved within 1-2 weeks, almost all within 4 weeks. One patient died 2 weeks after their 2nd denosumab dose from an unrelated cause - adjusted calcium was 2.16 just prior to death. Additional oral calcium was given in two patients; in one of these, hypocalcaemia recurred after a subsequent injection despite additional supplements, and denosumab was discontinued. Conclusion In a real-world setting, hypocalcaemia after denosumab in patients with reduced renal function (not on renal replacement therapy) is generally mild and rarely requires treatment. Disclosure S.A. Hardcastle: Other; S.H. received conference fee funding from Lilly (UK) in 2018. R. Alshakh: None. J. Webb: None. S. Warren: None. T. Ahmed: None.

To Decline or Accept: A Guide for Determining the Legitimacy of Academic Conference Invitations.

After the rise of predatory journals characterized by false claims of legitimacy and a pay-to-publish model, similar "predatory conferences" have become increasingly common. The email inbox of an academic physician can be filled with daily announcements encouraging conference attendance, abstract submission, and often panel or keynote speaker invitations. It therefore becomes important for the plastic surgeon to be able to discern whether these invitations are from "predatory" conferences or legitimate career advancement opportunities, especially early in practice. To aid the invited physician in determining the legitimacy of a conference, we aimed to characterize objective features of conferences for which email invitations have been received and use this information to build a decision-making guide. We analyzed all conference invitations received by the email of one academic plastic surgeon in a 4-month period. These conferences were organized into 3 groups based on affiliation with known professional societies. The following information was collected if available: affiliation with a professional society, type of invitation, conference location, conference format (in-person, virtual, or hybrid), conference title, conference fees, conference organizer, associated journals or publishers, abstract journal submission, grammar, headshots, time to abstract review, and acceptance. There were 56 unique conference invitations. These were categorized into 15 affiliated conferences, 28 unaffiliated conferences, and 17 conferences of undetermined affiliation. Unaffiliated conferences were more likely to solicit speaker invitations ( P < 0.001), claim to be "international" ( P = 0.001), send emails with grammatical errors ( P < 0.001), use unprofessional headshots on the conference Web site ( P < 0.001), and have reduced virtual conference fees ( P = 0.0032) as compared with conferences affiliated with known professional societies. When comparing the attendance and presenter fees of in-person venues, there was no significant difference between affiliated and unaffiliated conferences ( P = 0.973, P = 0.604). Affiliated conferences were more likely to take place in the United States ( P = 0.014). We present a method to quickly assess the legitimacy of an academic meeting by way of a few important questions. Based on our findings, emails soliciting conference speakers, claims of international presence, grammatical errors, unprofessional headshots, and reduced virtual conference fees are all characteristics that should raise red flags.

Positive effects of amphiregulin on human oocyte maturation and its molecular drivers in patients with polycystic ovary syndrome.

Does use of medium containing amphiregulin improve meiotic maturation efficiency in oocytes of women with polycystic ovary syndrome (PCOS) undergoing in vitro maturation (IVM) preceded by a capacitation culture step capacitation IVM (CAPA-IVM)? Use of medium containing amphiregulin significantly increased the maturation rate from oocytes retrieved from follicles with diameters <6 or ≥6 mm pre-cultured in capacitation medium. Amphiregulin concentration in follicular fluid is correlated with human oocyte developmental competence. Amphiregulin added to the meiotic trigger has been shown to improve outcomes of IVM in a range of mammalian species. This prospective, randomized cohort study included 30 patients and was conducted at an academic infertility centre in Vietnam from April to December 2019. Patients with PCOS were included. In the first stage, sibling oocytes from each patient (671 in total) were allocated in equal numbers to maturation in medium with (CAPA-AREG) or without (CAPA-Control) amphiregulin 100 ng/ml. After a maturation check and fertilization using intracytoplasmic sperm injection (ICSI), all good quality Day 3 embryos were vitrified. Cumulus cells (CCs) from both groups were collected at the moment of ICSI denudation and underwent a molecular analysis to quantify key transcripts of oocyte maturation and to relate these to early embryo development. On return for frozen embryo transfer (second stage), patients were randomized to have either CAPA-AREG or CAPA-Control embryo(s) implanted. Where no embryo(s) from the randomized group were available, embryo(s) from the other group were transferred. The primary endpoint of the study was meiotic maturation efficiency (proportion of metaphase II [MII] oocytes; maturation rate). In the per-patient analysis, the number of MII oocytes was significantly higher in the CAPA-AREG group versus the CAPA-Control group (median [interquartile range] 7.0 [5.3, 8.0] versus 6.0 [4.0, 7.0]; P = 0.01). When each oocyte was evaluated, the maturation rate was also significantly higher in the CAPA-AREG group versus the CAPA-Control group (67.6% versus 55.2%; relative risk [RR] 1.22 [95% confidence interval (CI) 1.08-1.38]; P = 0.001). No other IVM or embryology outcomes differed significantly between the two groups. Rates of clinical pregnancy (66.7% versus 42.9%; RR 1.56 [95% CI 0.77-3.14]), ongoing pregnancy (53.3% versus 28.6%; RR 1.87 [95% CI 0.72-4.85]) and live birth (46.7% versus 28.6%; RR 1.63 [95% CI 0.61-4.39]) were numerically higher in the patients who had CAPA-AREG versus CAPA-Control embryos implanted, but each fertility and obstetric outcome did not differ significantly between the groups. In the CAPA-AREG group, there were significant shifts in CC expression of genes involved in steroidogenesis (STAR, 3BHSD), the ovulatory cascade (DUSP16, EGFR, HAS2, PTGR2, PTGS2, RPS6KA2), redox and glucose metabolism (CAT, GPX1, SOD2, SLC2A1, LDHA) and transcription (NRF2). The expression of three genes (TRPM7, VCAN and JUN) in CCs showed a significant correlation with embryo quality. This study included only Vietnamese women with PCOS, limiting the generalizability. Although 100 ng/ml amphiregulin addition to the maturation culture step significantly improved the MII rate, the sample size in this study was small, meaning that these findings should be considered as exploratory. Therefore, a larger patient cohort is needed to confirm whether the positive effects of amphiregulin translate into improved fertility outcomes in patients undergoing IVM. Data from this study confirm the beneficial effects of amphiregulin during IVM with respect to the trigger of oocyte maturation. The gene expression findings in cumulus indicate that multiple pathways might contribute to these beneficial effects and confirm the key role of the epidermal growth factor system in the stepwise acquisition of human oocyte competence. This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED; grant number FWO.106-YS.2017.02) and by the Fund for Research Flanders (FWO; grant number G.OD97.18N). L.N.V. has received speaker and conference fees from Merck, grants, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring. T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme and Ferring. J.S. reports speaker fees from Ferring Pharmaceuticals and Biomérieux Diagnostics and grants from FWO Flanders, is co-inventor on granted patents on CAPA-IVM methodologies in USA (US10392601B2), Europe (EP3234112B1) and Japan (JP 6806683 registered 08-12-2020) and is a co-shareholder of Lavima Fertility Inc., a spin-off company of the Vrije Universiteit Brussel (VUB, Brussels, Belgium). NA, TDP, AHL, MNHN, SR, FS, EA and UDTH report no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. NCT03915054.

Half: A Prospective Multi-Centre Phase II Clinical Trial Evaluating the Efficacy and Safety of Tyrosine Kinase Inhibitors' Discontinuation after Two-Step Dose Reduction in Patients with Chronic Myeloid Leukemia in Deep Molecular Remission

Background.Treatment-free remission (TFR) has become a new treatment goal for chronic myeloid leukemia (CML) patients. However, usually abrupt tyrosine kinase inhibitors (TKIs) therapy discontinuation has been successful only in about half of eligible patients and it can cause burdening TKI withdrawal syndrome (TWS) in about 30% of them. Moreover, any robust clinical or biological factor predictive for successful TFR has not been identified yet. On top of that, sustainable deep molecular response (DMR) as the main prerequisite for TKI discontinuation attempt is achieved only in 20-40% of patients. The majority of CML patients, therefore, need to be treated with the effective and well-tolerated drug for a long time or even life-long.Study design and methods.With the recognition of all these aspects, we designed a nationwide prospective investigator-initiated phase II clinical trial HALF (ClinicalTrials.gov NCT04147533) in order to evaluate efficacy and safety of TKI discontinuation after previous two-step dose reduction in patients with CML in DMR (Fig. 1). Step-wise TKI dose reduction, i.e. half of the standard during the first 6 months after study entry, and the same dose given alternatively (every other day) during the next 6 months, was derived from pharmacokinetics and experimental data as well as from clinical trials' results. We assume that the step-wise and eventually meaningful TKI dose reduction enables a higher rate of patients achieving successful TFR with less pronounce TWS, or even would represent a more reasonable and safer alternative to the complete and sudden TKI interruption. This unique nationwide academic project has been facilitated by hematological patients care centralization in the Czech Republic.A primary study objective is to evaluate the proportion of patients in major molecular response (MMR) at 6 and 12 months and in TFR at 18, 24, and 36 months after the study enrollment, respectively, and molecular recurrence-free survival at all mentioned time points as well. Main secondary and exploratory objectives are: to evaluate the proportion of patients loosing MMR and in whom MMR and MR4.0 would be re-achieved after TKI re-introduction, time to MMR and MR4.0 re-achievement, FFS, PFS, OS, TWS, and QoL assessment, predictive factors for successful TFR identification, quantification of BCR-ABL1 using digital droplet PCR at both the DNA and mRNA levels, immunological profiling, BCR-ABL1 kinetics mathematical modeling, assessment of TKI pharmacokinetics, clonal hematopoiesis and pharmaco-economics.Results.The study was launched in December 2019; however, due to the COVID-19 outbreak, patients' recruitment started on June 16, 2020. Here, characteristics of the first 74 patients included in the study until April 2021 are presented. There were 37 males and 37 females, with median age at the time of diagnosis of 53 years (range, 23-74) and at the time of the study entry of 67 years (range, 35-86). A median time of CML disease, TKI treatment, and DMR duration before the study initiation was as follows: 9.9 years (range, 4.4-22.5), 9.8 years (range, 4.2-20.2), and 7.3 years (range, 3.2-18.3), respectively. The ELTS score was low, intermediate, high and unknown in 62.2%, 21.6%, 13.5%, and 2.7% of patients, respectively. At the time of study entry, 58 patients (79.5%) were treated with imatinib, 10 (13.7%) with nilotinib, and 5 (6.8%) with dasatinib, respectively, whereas in 63 patients (86.3%) it was in the first line of therapy. With almost half of patients (48.6%), the TKI dose was already reduced at the time of study entry. With 10 (13.5%) patients, interferon-α treatment preceded TKI administration. At the time of this abstract preparation, on July 26, 2021, altogether 102 patients (from planned 150) have been enrolled in the study; 48 of them (47.1%) have already moved to the second de-escalation phase and 9 (8.8%) patients to the TFR phase. There were 2 cases of confirmed MMR loss (both in month 8 after the study entry) and no patient experienced symptoms resembling TWS.Conclusions.Despite the COVID-19 pandemic, the HALF study was successfully launched and initiated in the majority of centers, with 102 already included patients and continuing intensive enrolment. Based on our very preliminary results, the step-wise dose reduction seems to be an effective and safe approach. More included patients, longer follow-up and further analyses are needed in order to reach all set up objectives. [Display omitted] DisclosuresŽácková: Angelini: Consultancy, Speakers Bureau; Novartis: Speakers Bureau. Faber: Angelini: Consultancy, Other: conference fees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Other: conference fees, Research Funding, Speakers Bureau; Novartis: Consultancy, Other: conference fees, Research Funding, Speakers Bureau; Pfizer: Other: conference fees; TERUMO: Other: conference fees. Bělohlávková: Novartis: Consultancy; BMS/Celgene: Consultancy. Horňák: Angelini: Honoraria. Svobodník: Roche: Speakers Bureau; Janssen-Cilag: Speakers Bureau. Machová Poláková: Incyte: Consultancy; Angelini: Consultancy; Novartis: Research Funding. Mayer: Principia: Research Funding.

CAR-T Toxicity Management and Steroid Use in High-Grade B-Cell Lymphoma: Impact on Real-World Survival Outcomes in the UK

CAR-T Toxicity Management and Steroid Use in High-Grade B-Cell Lymphoma: Impact on Real-World Survival Outcomes in the UK

COVID-19 Infection of HSCT Recipients Is Associated with High Mortality but No Detectable Cytokine Storm at Presentation

IntroductionThe clinical manifestations of COVID-19 infection in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in multiple retrospective cohorts of patients, but there have been no prospective studies to date. Previous studies report that HSCT recipients are at higher risk, with cumulative incidence of death between 17-35%. Although an excessive pro-inflammatory viral response has been documented in the general population, its role in the immune incompetent HSCT setting has not been documented.We present a combined prospective and retrospective national study run through the UK IMPACT trial network to characterize the clinical and immunological features of COVID-19 infection in 96 adult and pediatric recipients of HSCT in the United Kingdom.MethodsHSCT recipients of any age and transplanted for any indication, with an RT-PCR-proven COVID-19 infection, were eligible for this study. Patients within 72 hours of COVID-19 diagnosis, who had not received cytokine-targeted treatment, were recruited to a prospective cohort. All other patients were eligible for a retrospective cohort. Prospective patients provided blood samples within 72 hours of COVID-19 diagnosis, and again within 72 hours of clinical deterioration (defined as requirement for oxygen administration) if applicable. Follow-up data were collected on patients 30 and 100 days after COVID-19 diagnosis.Results100 patients were recruited from 16 sites across the UK between May 2020-June 2021, comprising 12 in a prospective cohort and 88 recruited retrospectively. 96 patients were evaluable, as 4 proved ineligible post-registration. Patients were diagnosed with COVID-19 at a median of 11 months after HSCT. Patient/HSCT characteristics are shown Table 1.The most common symptoms associated with the onset of COVID-19 were fever in 8 prospective (73%) and 35 (41%) retrospective patients, followed by cough in 5 (45%) prospective and 35 (41%) retrospective patients and dyspnea in 4 (36%) prospective and 16 (19%) retrospective patients. 8 (73%) prospective and 40 (47%) retrospective patients were actively immunosuppressed at the time of COVID-19 infection. 16% of the patients had moderate/severe disease at baseline.At day 30 (±2 days) after COVID-19 diagnosis, 2 prospective and 8 retrospective patients continued to demonstrate SARS-CoV-2 positivity on respiratory PCR testing. The median time to viral clearance was 40 (IQR 17-78) days for the prospective and 34 (IQR 15-70) days for the retrospective cohort.Prolonged (more than 14 days) neutropenia was reported in 4 (5%) patients in the retrospective cohort, prolonged thrombocytopenia in 2 (18%) prospective and 11 (13%) retrospective patients. 1 retrospective patient developed secondary hemophagocytic lymphohistiocytosis, and graft rejection was reported in 1 (1%) retrospective patient, within 30 days of COVID-19 diagnosis.In the prospective cohort, 3 (27%) patients died, all by day 30, and all due to COVID-19. In the retrospective cohort, 13 (17%) patients died by day 30, rising to 18 (21%) by day 100, 61% of deaths were attributed to COVID-19.Lower baseline platelets (p=0.013, Mann-Whitney U test), lymphocytes (p=0.012), albumin (p=0.028), and higher baseline CRP (p=0.007), were seen in patients who died following COVID-19 diagnosis. Additionally, exploratory univariate logistic regression of the retrospective cohort found mortality at day 100 to be associated with increased age at diagnosis (OR 1.04, 95% CI 1.01-1.08, p=0.04), and no requirement compared with requirement for invasive ventilation (OR 0.02, 95% CI 0.00-0.16, p=0.001).The 11 prospective patients showed normal levels of interleukin (IL)-2, -4, -10, interferon gamma and tumor necrosis factor alpha at COVID-19 presentation. IL-6 was minimally raised (up to 127 pg/ml, nv<50) in 3/11 pts at presentation. Respiratory deterioration was not associated with detectable cytokine storm.ConclusionOur study confirms a significant mortality rate in patients affected by COVID-19 post HSCT and confirms age as well as requirement for invasive ventilation to be independent risk factors associated with death at day 100.Baseline laboratory data at disease presentation can identify patients at higher risk of COVID-19 related death.In the prospective cohort of our study, pathophysiology of the viral disease did not seem related to cytokine storm-mediated inflammation. [Display omitted] DisclosuresProtheroe: Jazz Pharmaceuticals: Honoraria; Astellas: Honoraria; Kite Gilead: Honoraria. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nicholson: BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees; Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.; Autolus: Patents & Royalties.

Leukemic Stem Cells of Monocytic AMLs Are Not-Resistant to BCL-2 Inhibition

Treatment with Hypomethylating agents (HMA) such as 5-Azazytidine (AZA) in combination with the BCL-2 inhibitor Venetoclax (VEN) has recently become the standard of care for AML patients unsuitable for intensive induction chemotherapy and shows results superior to treatment with AZA alone (DiNardo et al., 2020, NEJM). However upfront resistance and relapse following initial response remain major obstacles.It has recently been proposed that monocytic differentiation predicts resistance to AZA/VEN treatment in AML (Pei et al., 2020 Cancer Discovery). This appears to be due to increased expression of other anti-apoptotic proteins such as MCL-1 in monocytic AMLs, which conveys resistance to AZA/VEN therapy, as survival of leukemic cells in these patients is no longer dependent on BCL-2. However, an independent study found no impaired outcome in patients with monocytic AMLs treated with HMA/VEN (Maiti et al., 2020, Blood, ASH abstract).Here, we show that monocytic AML cell lines and bulk cells of monocytic primary AML cells are indeed intrinsically resistant to AZA/VEN treatment. However, in a collective of 30 patients treated with HMA/VEN at Heidelberg University Medical Center between 2018 and 2020, monocytic differentiation assessed by flow cytometry was not an independent risk factor for refractory disease. We hypothesized that the conflicting data may be caused by intra-patient heterogeneity of AZA/VEN sensivitity and assessed killing efficiency in various immunophenotypic subpopulations of 12 primary AML patient samples in vitro.The CD64 +CD11b +, differentiated blast population made up >50% of leukemic cells in monocytic and <20% in primitive samples and showed high levels of resistance to AZA/VEN therapy in both primitive and monocytic leukemias but did not engraft when transplanted into NSG mice, arguing they do not contain leukemic stem cells (LSC).In contrast, we found immature CD64 -CD11b - GPR56 + LSC to be sensitive to AZA/VEN treatment irrespective whether they were derived from monocytic or primitive types of primary AMLs. As expected, LSCs from either monocytic or primitive AMLs initiated disease in NSG mice, highlighting that targeting LSCs is essential for the effect of AML therapy.Next, we investigated expression of BCL-2, MCL-1 and BCL-xL in the same primary patient samples and observed high MCL-1 expression in monocytic AML samples. However, MCL-1 expression was restricted to the CD64 +CD11b + population whereas in the LSC sub-populations robust expression of BCL-2 but low levels of MCL-1 and BCL-xL were detected, independent of whether monocytic or primitive AMLs were analyzed.To further validate the sensitivity of LSCs of monocytic AML to BCL-2-I, we established a platform combining BH-3 profiling with multi-color flow cytometry, allowing for single cell assessment of cellular dependencies on independent apoptotic pathways. We found that LSCs of both AML types show high VEN/BAD but low MS-1 induced apoptosis, functionally confirming the expression patterns of BCL-2 and MCL-1. As LSCs are rare in monocytic samples, investigation of samples in bulk are dominated by MCL-1 expressing and resistant non-LSCs, explaining the overall higher MCL-1 expression/survival of monocytic compared to immature AML cells. However, our data uncovers sensitivity of LSCs to AZA/VEN independent of overall monocytic or primitive sample classification and provide a mechanistic explanation for the clinical data of Maiti et al. and our Heidelberg AML collective, which found no increased resistance of monocytic AMLs to AZA/VEN treatment. DisclosuresUnglaub: JazzPharma: Consultancy, Other: travel costs/ conference fee; Novartis: Consultancy, Other: travel costs/ conference fee. Schlenk: Abbvie: Honoraria; Agios: Honoraria; Astellas: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Hexal: Honoraria; Neovio Biotech: Honoraria; Novartis: Honoraria; Pfizer: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding; AstraZeneca: Research Funding; Boehringer Ingelheim: Research Funding. Müller-Tidow: Janssen: Consultancy, Research Funding; Bioline: Research Funding; Pfizer: Research Funding.

Venetoclax-Azacitidine As Salvage Therapy and Bridge to Allogeneic Cell Transplantation in Relapsed/Refractory AML Compared to Historical Data of the SAL Registry Study

Venetoclax-Azacitidine As Salvage Therapy and Bridge to Allogeneic Cell Transplantation in Relapsed/Refractory AML Compared to Historical Data of the SAL Registry Study

Real-World Experience of CPX-351 As First-Line Treatment in 188 Patients with Acute Myeloid Leukemia

Real-World Experience of CPX-351 As First-Line Treatment in 188 Patients with Acute Myeloid Leukemia

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Early Integration of High Dose Methotrexate to Frontline DLBCL Therapy Does Not Impact CNS Relapse Compared to End of Treatment Delivery: A Multicentre International Analysis of 1384 Patients

Early Integration of High Dose Methotrexate to Frontline DLBCL Therapy Does Not Impact CNS Relapse Compared to End of Treatment Delivery: A Multicentre International Analysis of 1384 Patients

Two-Year Landmark Survival Analysis after Allogeneic Hematopoietic Cell Transplantation in Acute Lymphoblastic Leukemia: An Analysis from the ALWP of the EBMT

BackgroundLong-term survival and late mortality risk compared to general population for patients (pts) who underwent an allogeneic hematopoietic cell transplant (HCT) is unknown. We analyzed long-term outcomes of 2-year (yr) HCT survivors with acute lymphoblastic leukemia (ALL).MethodsAdult pts with ALL who were alive and relapse-free at 2 yrs after first HCT from 2005-2012 were included. We excluded patients who had a cord blood transplant and ex vivo T cell depletion (TCD). Relative survival analysis was used to estimate HCT-related crude mortality taking into account for background population mortality rates of the general population, matched for age, sex, and country in the year of HCT (www.mortality.org).ResultsA total of 2701 pts were included with a median follow up interval of 99 months and median age of 34 (range 18 - 73.5) yrs. The majority (78.6%) of pts were in 1 st complete remission (CR1) with undetectable MRD (68.3%). There were similar numbers of matched sibling donor (MSD) (43.7%) and unrelated donor transplants (MUD) (53.2%). Most pts received myeloablative conditioning (MAC) (86.5%) and peripheral blood (PB) grafts (75.7%) without in vivo TCD (55.7%).The 10-yr probability for overall survival (OS) and leukemia-free survival (LFS) was 81.3% and 78.2%, respectively. Cumulative incidence of disease relapse and non-relapse mortality (NRM) at 10 years was 9.9% and 11.9%, respectively. The probability of chronic GVHD-relapse-free survival (cGRFS) at 10-yrs was 73.3% (Figure 1). Relapsed ALL and chronic GVHD were common causes of late mortality accounting for 33.9% and 29% of reported deaths, respectively, followed by infection and secondary malignancy. For patients transplanted in countries with available mortality data (92% of patients in our cohort), the probability of dying from another cause is negligible at 1.5% compared to the probability of dying from HCT (16.8%) 10 years after HCT (Figure 1F).ConclusionsIn a large registry-based study, we showed excellent long-term survival of 81.3% at 10-yr among the 2-yr survivors of HCT for ALL. There was no difference in long term outcomes with respect to conditioning intensity, but utilization of BM graft and in vivo TCD resulted in lower NRM, and better OS. Long-term mortality risk among HCT survivors remains significantly higher than expected for the general age-matched population. [Display omitted] DisclosuresLabopin: Jazz Pharmaceuticals: Honoraria. Schroeder: Celgene: Honoraria, Other: Travel support, Research Funding. Bethge: Miltenyi Biotec: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Kite-Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Nicholson: Pfizer: Consultancy; BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees. Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Peric: Therakos, Servier, MSD, Astellas, Novartis, Abbvie, Pfizer: Honoraria. Dholaria: Janssen: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Jazz: Speakers Bureau; MEI: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; Celgene: Speakers Bureau. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Cost Evaluation Study of Management and Surveillance, and Review of the Recent USA and UK Guidelines

IntroductionBreast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell lymphoma associated with textured breast implants, recently recognized by the revised WHO Classification. Recommended management for BIA-ALCL involves a multidisciplinary team (MDT) approach with breast surgery, haemato-oncology, pathology, radiology and oncoplastic input. Definitive management for the 'effusion-only' subset is surgical implant and capsule removal; systemic therapy is reserved for 'mass-forming' and 'advanced-disease' cohorts. Overall prognosis is excellent with the vast majority achieving remission.Although the diagnostic and treatment paradigm is established, post treatment surveillance and follow-up guidance varies widely (globally); over-utilisation of imaging tests compromises the patient pathway, impacts limited health-care resources and is associated financial burdens on patients and providers. Recently, newly published consensus guidelines (UK MHRA and USA NCCN clarify follow-up and surveillance imaging (Table 1).The aim of this study was to review our BIA-ALCL specialist centre institutional practise; to quantify the direct economic cost (EC) of imaging surveillance and indirect EC of outpatient clinic (OPC) assessment compared EC if recent guidelines were followed. The secondary aim is to highlight and raise awareness of the latest international guidance to promote the standardisation of practise.MethodsA retrospective analysis of a prospectively maintained patient database between July 2015 to October 2019 was conducted, with Institutional Review Board Approval. Data collection included patient demographics, tumour subset, treatment, clinical and imaging surveillance. Follow-up and imaging undertaken for symptomatic concerns / non-BIA-ALCL related pathology was excluded. Imaging costs were calculated using UK NHS tariffs.ResultsEleven patients were treated for BIA-ALCL during the study period, with a median age of 49 at diagnosis (range 30-82years). Patients were diagnosed with: effusion-only (n=7), effusion and mass (n=2), mass-only (n=2) subtypes, at a median time of eleven years from implant insertion (IQR 8-12). All patients underwent explantation and en-bloc capsulectomy, with 1 patient required neo-adjuvant (CHOP, Brentuximab) and 1 adjuvant (CHOP) therapy (CHOP. Surveillance with imaging and OPC detected no disease recurrence to date (overall median follow-up 38 months, IQR 12-47). Post treatment episodes of surveillance imaging or follow-up related to patient symptoms were excluded.8 patients underwent surveillance imaging at our institute (Table 2). Total cost of imaging was £10,396 ($14,396) with a median cost of £1,953 ($2,705) per patient [IQR £526-2029 ($728-2,810)].7 patients had completed at least 24 months follow-up since surgery during the study period (Table 3), with 3 patients having not yet completed their follow-up period of two years. Of those with completed follow-up, the median OPC follow-up per patient was 48 months (IQR 38-52), median number of OPC was 7 (IQR 6-11) and the median cost of clinic review was £982 (IQR 804-1395). The surplus cost per patient compared with recommended follow-up was £118 ($164) [IQR £0-531 ($0-738)].ConclusionsOur data shows the variable BIA-ALCL surveillance practise pattern and the associated additional direct and indirect EC of unnecessary asymptomatic surveillance imaging, with an excessive number of follow-up OPC and period of clinical follow-up after complete remission. With no recurrence detected in our patient cohort to date, this data supports the new UK and updated USA NCCN Guidelines (extrapolated from data in other NHLs, and analogous to principles of the ASH Choosing Wisely Campaign) that routine post-treatment surveillance imaging should not be performed in BIA-ALCL patients. Routine asymptomatic post-treatment surveillance imaging is clinically unnecessary and potentially leads to a 'Cascade Effect' of further tests, with increased radiation exposure, excess costs and impact on limited health-care resources. We also support open-access follow-up for patients in remission, to reduce unnecessary follow up appointments. With UK and USA guidelines now available for BIA-ALCL, we support training and education of health-care professionals, global consensus guidelines and a registry, for this rare however increasingly recognised new entity. [Display omitted] DisclosuresIyengar: Takeda: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: conference support; Janssen: Other: conference support, Speakers Bureau. Nicholson: Pfizer: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; BMS/Celgene: Consultancy; Novartis: Consultancy, Other: Conference fees. El-Sharkawi: Kyowa Kirin: Other: Ad boards; Beigene: Other: Ad boards; ASTEX: Other: Ad boards; Novartis: Other: Travel Support; Takeda: Honoraria; Roche: Honoraria; Janssen: Honoraria, Other: Ad boards; AstraZeneca: Honoraria, Other: Ad boards; AbbVie: Honoraria, Other: Travel Support, Ad boards. Tasoulis: BMJ: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cunningham: Roche: Research Funding; Clovis Oncology: Research Funding; Celgene: Research Funding; Eli Lilly: Research Funding; Bayer: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees; 4SC: Research Funding; AstraZeneca: Research Funding; MedImmune: Research Funding.

Outcomes of Children and Young Adults with Acute Lymphoblastic Leukaemia Administered Inotuzumab Pre CAR-T Therapy

Introduction:Immunotherapies like Inotuzumab ozogamicin (InO), Blinatumomab and Chimeric antigen receptor T cell therapy (CAR-T) have revolutionized outcomes in patients with Relapse/Refractory Acute Lymphoblastic Leukaemia (R/R ALL) with event free survival (EFS) of 50% at 1 year (Maude et al. 2018).Optimal phasing of these agents has not been clearly defined and depends on antigen expression on blasts, CNS status, T cell number and prior disease response. InO, a CD22 targeting antibody-drug conjugate has proven efficacy in adults (Kantarjian et al., 2016) and children as a bridge to allogeneic stem cell transplantation (allo-SCT) with a favourable toxicity profile (Brivio et al. 2021). However, outcomes following the use of InO prior to CAR-T therapy are still not established.This study provides a retrospective analysis of children and young adults who received InO as part of pre-CAR-T management (before leucapheresis or as bridging therapy to CAR-T infusion).Methods:Patients aged 0-25years with R/R ALL were eligible for the study if they received InO pre-CAR-T therapy. Retrospective data collection was performed using a standardised form from CAR-T centres in the UK. Response to CAR-T therapy and/or relapse was evaluated at 1, 3, 6, 12 months or at last follow-up. Results were compared to a control cohort of R/R ALL patients treated with tisagenlecleucel but without preceding InO, over a contemporaneous period, at the largest paediatric CAR-T centre in the UK.Results:Fourteen patients from 5 paediatric and young adult centres in the UK received InO after screening for CAR-T therapy. InO was used pre-leucapheresis, as bridging and for both in 2, 11 and 1 respectively. Two were excluded from outcome analysis (1 adolescent with Trisomy 21 and transfusion induced hepatic siderosis died due to VOD while awaiting CAR-T production and 1 failed CAR-T manufacture despite achieving an adequate T cell harvest as per manufacturer guidance). Twelve (85%) patients were able to receive CAR-T infusion at a median of 1 month (range 0.7-5.6 months) from first InO dose. InO was well tolerated with 21% developing febrile neutropenia and grade 4 cytopenias. Use of InO pre-leucapheresis led to successful manufacture of CAR-T cells in 2/3 (66%). InO group was compared with 27 children who received CAR-T without preceding InO over the same time period. Table 1 summarises patient and CAR-T characteristics of the two groups which were comparable. Median follow-up of the InO and non-InO groups was 10 months (range 2.8- 30.1 months).In the InO group(n=12), 3 (25%) remained leukemia free at last follow up. Nine patients (75%) relapsed. All relapses occurred within 6 months from CAR-T infusion. Seven (58%) of those who relapsed died at a median of 7.8 months post CAR-T infusion and 2 (16.6%) were salvaged with further therapy. Subsequent therapy (alternate CAR-T and/or allo-SCT) was carried out in 4/12 (33%) patients in the InO group and in 5/27 (18.5%) in the non-InO group (p= 0.2). EFS was significantly higher in the non-InO group (53% vs 12%, p=0.0009), as was OS (86% vs 13%, p=0.004) (Figure 1).Conclusion:This study provides a direct comparison between two contemporaneously treated cohorts with R/R ALL receiving CAR-T therapy. InO prior to CAR T cell therapy was well tolerated despite the cohort being heavily pre-treated except for one patient who developed fatal VOD prior to CAR T cell infusion. InO was given for disease debulking, rather than to achieve MRD negativity and hence majority of the cohort (75%) received only 1 dose of InO in bridging rather than the usual schedule of three doses weekly per cycle.Outcomes for the non-InO group were comparable to those treated on the ELIANA study but the OS of the InO group was significantly lower (13% vs 86% p= 0.004). Potential reasons include an impact of InO on function of CAR-T cells in vivo or a deleterious effect of InO on the B cell compartment such that CAR-T cells prove less effective. Due to the retrospective nature of the study, it is possible there was an inherent bias to use InO in patients with more resistant disease, although the very comparable pre CAR-T bone marrow disease burden in each group suggests this was not the case. The small size of the cohorts may also have exaggerated differences in outcome.Ultimately, randomised controlled studies of InO pre-CAR-T are required before firm conclusions about its impact on outcomes post CAR-T therapy can be ascertained. [Display omitted] DisclosuresSharplin: Kite Gilead: Honoraria; Novartis: Other: Travel Support. Nicholson: BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees; Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.; Autolus: Patents & Royalties. Ghorashian: Novartis: Honoraria; UCLB: Patents & Royalties.

Biological and Classical Prognostic Factors with Impact on Overall Survival in Patients with Early Stage (I/II) Diffuse Large B-Cell Lymphoma: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL.Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or II. The variables analyzed included demographic and clinical variables (e.g., age, ECOG performance status), the International Prognostic Index (IPI), and laboratory variables such as serum albumin, serum lactate dehydrogenase (LDH), serum beta-2-microglobulin, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (LNR), and the platelet-lymphocyte ratio (PLR). To determine the variables associated with mortality, univariate and multivariate Cox regression (step-wise type) analysis was performed. Kaplan-Meier and log-rank test were used for survival analysis. Outcomes with a p-value <0.05 were considered statistically significant.Results: We identified 1,375 patients with DLBCL; 503 were identified as early stage DLBCL of whom 498 had sufficient data for analysis. Almost all cases (n=483, 96%) had nodal disease as the primary site, and 15 (4%) extranodal, all within the gastrointestinal tract. There was a slight female predominance (51.8%). The median age at diagnosis was 64 (IQR: 50 -73) with 57.4% older than >65 years. ECOG performance status of <2 was seen in 77.2% of cases; elevated serum LDH in 32.4%; and elevated serum beta-2-microglobulin in 5.6% (n=11/192). Based on previous data, we evaluated and calculated variables that have been suggested as independent negative prognostic factors for overall survival; the proportion of patients with serum albumin <3.5 mg/dL; LMR <2, NLR >4, and PLR >376 was 34.4%, 10.3%, 9.2%, and 4.7% respectively. With a median follow-up of 45 months, the median 5-year overall survival (OS) rate was 72%. The therapy approaches used, response rates and outcomes with these approaches will be presented at the meeting. Results of the univariate and multivariate analysis are summarized in Table 1. We found that age over 65, ECOG performance status, serum albumin level, beta-2-microglobulin level, LDH ratio, LMR, NLR, PLR, and BCL-2 positivity by immunohistochemistry (IHC) were prognostic factors for OS in the univariate analysis. However, in the multivariate analysis, only NLR, serum albumin level and ECOG performance status were independent factor for worse prognosis. Survival rates were significantly shorter in patients with serum albumin <3.5 g/dL (5-year OS of 49% versus 79%, respectively; p<0.0001); NLR >4 (5-year OS of 46% versus 73%, respectively: p=0.0013); and ECOG performance status ≥2 (5-year OS of 51% versus 74%, respectively; p<0.0001) (Figures 1 to 3).Conclusion: In this large cohort of Latin American patients with early stage DLBCL most patients were older than 65, had nodal disease as the primary site, good performance status, with only a third of patients exhibiting elevated LDH. Moreover, we found serum albumin <3.5 g/dL, NLR >4 and ECOG ≥2 as negative prognostic factors for poor survival in early stage DLBCL. We are currently validating our findings in a prospective cohort of Latin American DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. [Display omitted] DisclosuresOtero: Astra Zeneca: Current Employment. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.