Conference Fees Research Articles

A Novel Prognostic Index for Patients with EBV-DLBCL NOS: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. Current prognostic models such as the Oyama and the International Prognostic Index (IPI) score have limited prognostic value in this patient population. Therefore, we aim to evaluate the ability of these models to risk stratify patients and propose a novel prognostic model in the largest cohort of Latin American patients with EBV+ DLBCL, NOS.Methods: This retrospective cohort study included patients ≥18 years from six Latin American countries diagnosed and treated at tertiary centers from 2010 to 2020. Hematopathologists at each institution reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL, NOS. We collected clinicopathological data by reviewing the medical records of the patients. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last visit. The secondary endpoint, progression-free survival (PFS), was defined as the time from diagnosis until death, progression, or last visit. Our novel model (Grupo de Estudio Latinomericano de Linfoproliferativos [GELL] Score) includes the Eastern Cooperative Oncology Group (ECOG) performance status ≥2, extranodal involvement >1, serum albumin <3.5 g/dL, serum lactate dehydrogenase (LDH) above the upper limit of normal, and platelet-to-lymphocyte ratio >455. We assigned a value of 1 to each of the abovementioned elements in the score and classified the patients as low (0 points), intermediate (1-2 points), and high (3-5) risk. OS and PFS probabilities were computed with the Kaplan-Meier method and compared with the log-rank test. We used Cox regression to evaluate the proportional hazard ratios (HR) of each score for our study outcomes. The C-index was employed to measure discrimination of each model. We used cross-validation to evaluate the model performance.Results: A total of 154 patients with EBV+ DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with a slight male predominance (53%). EBER was positive in all cases (range 1-100%). Clinically, 39% presented ECOG ≥2, 57% had B symptoms, 50% had an extranodal disease as a primary tumor, and 71% had Ann Arbor stage III/IV. Fifty-one percent of the patients had an elevated LDH level, and 43% had albumin <3.5 g/dL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was administered in 79% of individuals as first-line treatment. The overall response rate was 80% (62% complete response and 18% partial response). With a median follow-up of 61 months, the 5-year OS and PFS rates were 61% and 47%, respectively. The 5-year OS rates of patients with low, intermediate, and high-risk disease according to the GELL score was 90%, 59%, and 33%, respectively (Fig 1A). The 5-year PFS rates were 82%, 39%, and 23%, respectively (Fig 2A). Table 1 shows the Cox regression and the discrimination analysis for each of the scores. The GELL score has the highest discriminatory index for OS and PFS compared to the IPI, Revised-IPI, National Comprehensive Cancer Network-IPI, and the Oyama score (Figure 1 and 2).Conclusions: This study proposes a novel score for risk stratification of patients with EBV+ DLBCL, NOS. The GELL score appears to better discriminate OS and PFS than previous scores. Our results should be validated in an independent prospective cohort. [Display omitted] DisclosuresRamirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. 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.

Clinicopathological Features and Outcomes of EBV Positive and Negative DLBCL: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Introduction: Studies conducted in the pre-rituximab era found EBV positive diffuse large B-cell lymphoma (EBV+ DLBCL) as a disctinct entity carrying a dismal prognosis when compared with EBV negative (EBV-) DLBCL cases. However, studies evaluating this disparity in the rituximab era are lacking. Therefore, we aim to investigate the clinicopathological features and outcomes patterns among EBV+ and EBV- DLBCL managed in the modern era.Methods: We retrospectively analyzed patients 18 years and older diagnosed with DLBCL between 2006 to 2020. Seven centers from the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) participated in the study. Hematopathologists at each participating institution reviewed the pathological samples to confirm the diagnosis of EBV+ or EBV- DLBCL, not otherwise specified (NOS). EBV infection was confirmed with a positive EBER test ≥1%. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last follow up. The secondary endpoint was progression-free survival (PFS) defined as the time from diagnosis until death, progression, or last follow up. OS and PFS probabilities were computed with the Kaplan-Meier method and compared using the log-rank test. We used Cox regression analysis to evaluate the proportional hazard ratios (HRs) of each score for our study outcomes. Outcomes with a p-value <0.05 were considered statistically significant.Results: A total of 119 patients with EBV+ DLBCL, NOS and 122 patients with EBV- DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with an slight female (53%) predominance. Most cases (68%) had advanced stage (III/IV) at diagnosis. EBV+ DLBCL patients had higher-risk clinical features compared with EBV- DBCL: 34% presented ECOG performance status ≥2 (vs 18%, p=0.010), 45% had poor risk R-IPI score (vs 29%, p=0.03), 47% had high and high-intermediate risk NCCN IPI score (vs 40%, p=0.002). Germinal center B-cell was the most common phenotype in both groups (46% each); non-germinal center was more common in EBV+ (44%) than EBV- (34%). All patients received either R-CHOP (95%) or R-EPOCH (5%) as first-line treatment. The overall response rate was 91% for EBV- DLBCL (complete response, CR 81%) compared to 74% for EBV+ DLBCL (CR 65%, p=0.015). With a median follow-up of 60 months, the 5-year OS rates for EBV+ and EBV- DLBCL were 64% and 75% (p=0.062; Fig 1A), respectively; whereas the 5-year PFS rates for EBV+ and EBV- DLBCL were 53% and 68% (p=0.031; Fig 1B), respectively. In the univariate analysis, ECOG ≥2, extranodal involvement >1, elevated serum lactate dehydrogenase (LDH), and serum albumin <3.5 g/dL were statistically significant for OS (Table 1). On the other hand, EBV+ status, ECOG performance status ≥2, extranodal involvement >1, elevated serum LDH, and serum albumin <3.5 g/dL were significant predictors for PFS. In the multivariate analysis, no variable was statistically significant for OS or PFS (Table 1).Conclusions: In this large cohort of Latin American patients with EBV+ DLBCL, we found poor clinical features in EBV+ compared to EBV-DLBCL cases. Although shorter PFS was found in EBV+ DLBCL cases, in the multivariate analysis we could not identify EBV status as an independent risk factor for worse survival. Our results suggest that in the rituximab era, there has been an improvement on the survival outcomes of EBV+ DLBCL, NOS patients managed with chemoimmunotherapy. We are currently validating our findings in a prospective cohort of DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality and relapse. [Display omitted] DisclosuresRamirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Abbvie: Other: conference support and fees ; Roche: 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.

Clinical and Subclinical Cardiotoxicity after Hematopoietic Stem Cell Transplantation

Introduction:Cardiovascular disease is the leading cause of death, in Uruguay it corresponds to 30%. To the known risk factors, the use of QT and RT are added. The improvement in response and overall survival of hematologic patients allow a longer time to develop cardiovascular complications. Cardiotoxicity has been extensively studied in the context of breast cancer and the use of anthracyclines; however, there are very few data on hematopoietic stem cell transplantation (HSCT).Objective:Assess subclinical myocardial damage by measuring biomarkers and echocardiography and identify patients at high risk of developing cardiotoxicity after HSCT.Methods:This is a prospective, single-center study between April 2017 and November 2020. Population: adult patients admitted in the British Hospital Transplant Unit, Montevideo Uruguay to receive either an autologous or allogeneic HSCT. Measurement: cardiac biomarkers (pro-BNP, Troponin T, Troponin I and CPK) at admission, D1, D14 and D30. Echocardiograms were performed on admission and at D30 by the same team of 3 echocardiographers with the same machine. It was repeated at D100 if some alteration was seen.Results:We included 158 transplants: 148 autologous and 10 allogeneic. The characteristics of the population and results are shown in Table 1. 126 raised some biomarker during the first 100 days (79.7%). Pro-BNP is the biomarker that most frequently rises after admission until day 100: 125/158 (79.1%). The kinetics of the biomarkers are shown in Figure 1. Regarding echocardiograms, there were no patients with a cardiotoxicity criterion defined by: a decrease in LVEF of more than 10% to a value less than 53%. Regarding myocardial deformability, there was a reduction in strain between the initial echocardiogram and D30 in 76 patients of 116 patients with both determinations (65.5%). A reduction of 15% or more was evidenced in 18 (11.3%). Of them, 13 (72.2%) had elevated biomarkers in the first 100 days. Of the patients who did not have strain changes, 78.6% had elevated biomarkers. No statistically significant relationship was found between strain reduction and the presence or absence of elevated biomarkers in the first 100 days.With a median follow-up of 23.3 months (0.89-48.62), 11 (7%) developed clinical cardiotoxicity: hypertension 6, arrhythmia 4, pulmonary embolism 1, sudden death 1. We have strain data of 6/11 patients, and there was no reduction of 15%. Of the 11, 90.9% raised some biomarker during the 100 days. Median development time of cardiotoxicity: 10.3 months (0.03-36.6). 133 had one year follow up so, the incidence of clinical cardiotoxicity at 1 year is 4.5%.There were no differences in elevated biomarkers in the first 100 days and use of Melphalan (p = 0.096) however, there was a difference with BEAM versus other plans, p = 0.035. The reduction in strain at day 30 was not influenced by Melphalan or BEAM.Patients with subclinical myocardial damage were older than those without it: mean age: 56.7 +/- 11.2 versus 44.1 +/- 13.1, p = 0.0001. There was no statistically significant difference between patients who had elevated biomarkers in the first 100 days versus those who did not in relation to a history of diabetes, hypertension, dyslipidemia, heart disease or previous use of anthracyclines. Either in patients with a 15% reduction in strain versus those without.This is one of the first studies worldwide that comprehensively evaluates cardiovascular function during HSCT. Given the small number of observed cardiac complications, greater follow-up of this subpopulation with elements of subclinical cardiotoxicity is required to determine if they are indeed predictive parameters of cardiovascular complications in the future in the transplant setting.Conclusions:Subclinical cardiotoxicity is common in transplantation: Pro-BNP is the biomarker that most frequently rises after admission until day 100: 79.1%. Strain reduction of 15% or more occurs in 11,3%. Subclinical myocardial damage parameters were not associated with type of conditioning, previous use of anthracyclines, comorbidities and clinical cardiotoxicity at 1 year. Clinical cardiotoxicity post HSCT is low, 4,5% at 1 year. We must do a longer-term follow-up in order to evaluate whether the combination of pro-BNP associated with strain reduction can be predictive factors of clinical cardiotoxicity. [Display omitted] DisclosuresOliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees .

The Impact of gain1q on Mutational Structure and Clonal Evolution in a Uniformly Treated High-Risk Series of Patients at First Relapse

The Impact of gain1q on Mutational Structure and Clonal Evolution in a Uniformly Treated High-Risk Series of Patients at First Relapse

Phenotypic High-Risk Disease in the Context of Carfilzomib and Lenalidomide Combination Induction Therapy for Newly Diagnosed Transplant-Eligible Myeloma Patients

Phenotypic High-Risk Disease in the Context of Carfilzomib and Lenalidomide Combination Induction Therapy for Newly Diagnosed Transplant-Eligible Myeloma Patients

Fitness, a UK Myeloma Research Alliance (UK-MRA) Frailty-Adjusted Therapy Study, Supports the Feasibility of Recruiting Frail Newly Diagnosed Myeloma Patients to Large Clinical Trials

Fitness, a UK Myeloma Research Alliance (UK-MRA) Frailty-Adjusted Therapy Study, Supports the Feasibility of Recruiting Frail Newly Diagnosed Myeloma Patients to Large Clinical Trials

Multistate Models Demonstrate That Lenalidomide Maintenance Enhances Survival By Prolonging Time in First Remission for Patients Treated in the UK NCRI Myeloma XI Randomised Trial

Multistate Models Demonstrate That Lenalidomide Maintenance Enhances Survival By Prolonging Time in First Remission for Patients Treated in the UK NCRI Myeloma XI Randomised Trial

The uneven distribution of fees for virtual academic conferences

This study examines factors of importance for the pricing of virtual academic conferences based on information on their quality attributes. Data are based on 76 virtual conferences held or planned to be held in the field of tourism and related fields between April 2020 and December 2021. The distribution of fees is skewed with a median price of US$61 and an average of US$126. One fourth of the conferences is free of charge, although there is a trend toward increased prices the longer the time elapse from the outbreak of the pandemic, ceteris paribus. Count data model estimations show that the conference fee depends on size, academic field, and location of the host. A one-day conference is on average US$60 cheaper than a two-day event while pure tourism conferences are on average US$34 more expensive than those in related fields. Conferences in the United Kingdom have the lowest fees while hybrid format is a factor of specific importance for the pure tourism events. Reputation of the host university and whether the conference is held by an association are aspects of no significance for the fee.

Establishment of CORONET: COVID-19 Risk in Oncology Evaluation Tool to Identify Cancer Patients at Low Versus High Risk of Severe Complications of COVID-19 Infection Upon Presentation to Hospital

Establishment of CORONET: COVID-19 Risk in Oncology Evaluation Tool to Identify Cancer Patients at Low Versus High Risk of Severe Complications of COVID-19 Infection Upon Presentation to Hospital

Micronized progesterone plus dydrogesterone versus micronized progesterone alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospective cohort study.

Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone? Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone. Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET. Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020. We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached ≥8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks' gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints. The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99-1.27, P = 0.06; multivariate analysis RR 1.30 (95% CI 1.01-1.68), P = 0.042), with a statistically significant lower rate of miscarriage at <12 weeks in the progesterone + dydrogesterone versus progesterone group (3.4% versus 6.6%; RR 0.51, 95% CI 0.32-0.83; P = 0.009). Birth weight of both singletons (2971.0 ± 628.4 versus 3118.8 ± 559.2 g; P = 0.004) and twins (2175.5 ± 494.8 versus 2494.2 ± 584.7; P = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group. The main limitations of the study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability. Our findings study suggest a role for oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles to reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice. This study received no external funding. LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has received scientific board fees from Ferring and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant. NCT0399876.

P179 Perpetual dilemma: international multicentre study correlating BASDAI and ASDAS (CRP) as a marker of disease activity in spondyloarthritis

Abstract Background/Aims While BASDAI is one of the most widely used tool it has limited face and construct validity. ASDAS on the other hand is considered more objective ,however in absence of blood investigations, it might not be an ideal measure. We aimed to study correlation and agreement between ASDAS-CRP with BASDAI score. We correlated these outcome measures with MRI activity Methods This was a multi-centre study, conducted at rheumatology department of two teaching hospitals in United Kingdom and India. Anonymised data of all consecutive patients with the clinical diagnosis of SpA were analysed. We compared outcome measure variables ASDAS-CRP with BASDAI at baseline and follow-up with subgroup analysis of BASDAI cutoff of 4. We also analysed radiological parameters and compared disease activity of patients with active changes of SpA in MRI versus those with inactive changes . SPSS software and Cohen’s kappa statistics used Results Total 250 patients with SpA were analysed with median age of 34 years and total duration of 5.9 +6 years. Mean BASDAI 4.9 +8.8, Mean ASDAS-CRP 3.04 + 3.5, Mean CRP 19.32 +12.8 mg/l. The Correlation between BASDAI and ASDAS-CRP (r) was 0.76 and the correlation coefficient of agreement between ASDAS-CRP and BASDAI &amp;gt;4 was 0.75.The cutoff point of ASDAS with the best agreement with BASDAI was 3.5 (global agreement 78%, kappa 0.55). Both BASDAI and ASDAS showed a higher correlation with patient’s global assessment (PtGA) (r = 0.82 and 0.74, respectively) than with physician’s global assessment(PhyGA) (r = 0.76 and 0.7) The discriminant validity analysis showed that both ASDAS and BASDAI were able to discriminate patients above and below median PtGA (d = 1.15 &amp;d=1.3) and PhyGA (d = 0.75 and d = 0.9) respectively however BASDAI was better than ASDAS to discriminate patients above and below the median PhyGA (p = 0.05)60 patients were followed up with mean duration of follow-up of 6.2 +1.6 months. Both ASDAS and BASDAI decrease significantly (p = 0.03 and 0.02 respectively) however effect size was greater for ASDAS(0.8) than BASDAI (0.6). There was no difference noted in the degree of spinal inflammation as evidenced by MRI when patients with BASDAI &amp;gt;4 were compared to &amp;lt; 4. (p = 0.43, OR 0.6). The correlation between ASDAS and BASDAI was much higher in patients with active MRI lesions (r = 0.84), without any difference in CRP or BASDAI (p = 0.8 and p = 0.66 respectively) Conclusion This is a first study involving India and UK, which systematically compares the disease activity and outcome measures. Although BASDAI and ASDAS correlate well, the agreement is better for patients with high disease activity. ASDAS is more sensitive to change and shows larger effect size on follow-up. The outcome measures correlated more with active MRI lesions. Thus the cutoff value of BASDAI &amp;gt;4 for active disease might need a revision in clinical practice Disclosure N. Jain: None. S. Pandya: None. P. Srivastava: None. D. Shukla: None. A. Moorthy: Honoraria; Speaker and Conference fee MSD, Novartis Abbvie.

P198 Efficacy and safety of secukinumab in ankylosing spondylitis: real-world data from Midlands Ankylosing Spondylitis Collaboration (MASC)

Abstract Background/Aims Secukinumab is an interleukin-17 inhibitor has been found to be effective in the treatment of ankylosing spondylitis (AS) in studies, including phase 3 clinical trials, however these are conducted in highly selected patients and it is important to confirm the efficacy and safety in a real world data. Response to secukinumab should be assessed after 16-weeks and continued if there has been sufficient response to treatment according to the BASDAI and spinal VAS scores. Methods This was a multicentre cross-sectional observational study in collaboration with Midland Ankylosing Spondylitis Collaboration. Consecutive baseline and 16th week data of all AS patients on Secukinumab from 2017 to 2019 were collected and analysed to assess treatment response. All data were compiled in excel sheets and analysed using Medcalc calculator. Data were collected from collaborative efforts of the Royal Wolverhampton NHS trust, Queen’s Hospital (Burton on Trent), Leicester Royal Infirmary and Robert Jones and Agnes Hunt hospital. Results Total 92 patients with radiographic AS on standard dose of secukinumab were included at baseline and 88 were followed up till week 16. Mean age was 45.9(SD ± 15) (Median=44years) and 67% were male. Baseline Mean BASDAI was 7 (SD ± 1.7); Mean CRP was 16.6 (SD ± 11.2), Mean VAS was 7.6(SD ± 1.6). There was statistical significant change in BASDAI, VAS and CRP levels at week 16th. ΔBASDAI=2.2 (SD ± 2) (p = 0.002), ΔVAS=3.2 (SD ± 2.1) (p = 0.001), ΔCRP=6.9 (SD ± 17) (p = 0.03). At 16th week, 68% had clinical improvement while 4 patients discontinued therapy (2-colitis, 1-uveitis and 1-patient choice). 10% overall had some adverse effects with most common being upper respiratory tract infection. We also compared patients with previous anti-TNF exposure (TE) to Anti-TNF naïve (TN). 63% were in TE group vs 37% in TN. 69% of TE and 76% of TN showed clinical improvement at week 16.Mean ΔBASDAI was more in TN group vs TE (p = 0.01), however there was no difference in ΔVAS and ΔCRP levels. (p = 0.0 &amp; p = 0.2 respectively). Conclusion This multi-centre retrospective analysis found secukinumab to be clinically effective in 68% of patients with AS. There was significant improvement in BASDAI, VAS and CRP levels at week16. Compared to anti-TNF resistant patients, TNF-Naïve responded better to secukinumab, although both showed good clinical improvement. These findings support the use of secukinumab in the treatment of AS, as a first line therapy or for those who have failed anti-TNF therapy. Safety signals observed in the real-word data set were consistent with those seen in the clinical trials and the Summary of Product Characteristics. Disclosure N. Jain: None. R. Laxminarayan: Honoraria; Honorarium from Novartis, Lilly, Pfizer and Abvie. A. Moorthy: Honoraria; Speaker and conference fee MSD, Novartis, Abbvie. R. Amarasena: None. N. Cleaton: None. G. Kakade: None. A. Gunawardane: None. T. Khan: None. H. Sapkota: None. N. Barkham: Grants/research support; research funding from Novartis, Eli Lilly, UCB.

P185 Does BASDAI score correlate to MRI changes in ankylosing spondylarthritis?

Abstract Background/Aims The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is routinely used subjective outcome measurement of disease activity in Ankylosing Spondylitis (AS). BASDAI &amp;gt; 4 is used as a criterion for commencing anti-TNF therapy. Previous studies shown BASDAI correlation with MRI has been proven to be weak. We did this study to systemically compare clinical and radiological data of patients with AS and to look for the degree of correlation between BASDAI score and MRI changes positive for spondyloarthritis in our cohort of patients. Methods A retrospective analysis of AS patients attending Leicester spondylarthritis service at University Hospitals Leicester Trust (UHL) was carried out. Clinical characteristics such as HLA-B27 status, extra-articular features, family history of AS and CRP measurement were obtained from online systems and clinic letters. Online records were reviewed to see if patients had a MRI of the sacroiliac joints along with a BASDAI score at the time of MRI. Medcalc calculator was used for statistical analysis. Results A total of 106 patients were analysed with a mean age of 45.6 +/- 11.6 years (M = 62, F = 44) with mean BASDAI of 5.0 +/- 2.5. Mean CRP was 17.01+/- 30.4 (median CRP 6.5). 61% (n = 65) were HLA-B27 positive. 70 of 106 patients had a sacroiliac MRI scan which could be reviewed to a satisfactory level to determine whether disease is present or not. Two results were statistically significant when comparing active versus no active lesions on MRI: inflammatory back pain and anti-TNF therapy (Table 1). P185 Table 1:Comparison of clinical features in patients with active versus inactive lesions on MRI sacroiliac joint.Active lesions on MRI N = 45No active lesions on MRI N = 25P valueMean BASDAI (SD)5.0 (2.6)5.4(2.6)0.5Mean ASDAS CRP (SD)2.14(1.1)2.04(0.6)0.73Mean CRP (SD) mg/l14.7(21)17.8(33)0.645.5HLA-B2731180.Uveitis1190.3Inflammatory back pain40170.03Enthesitis820.3Peripheral Arthritis670.1Dactylitis010.2Psoriasis211Inflammatory bowel disease710.1Ethnicity: Caucasian37230.2Ethnicity: Asian820.3Age45.5 (10.2)50.5(11.3)0.06M: F26:1916:90.7Anti-TNF therapy1840.03BASDAI &amp;gt;428150.8BASDAI &amp;lt;417100.8BASDAI= Bath ankylosing spondylitis disease activity index, ASDAS= Ankylosing Spondylitis disease. CRP=C-reactive protein, HLA= human leucocyte antigen. Conclusion BASDAI score did not statistically correlate with the severity of inflammation as objectively observed on MRI. Only inflammatory back pain and anti-TNF therapy correlated with MRI disease activity. There was no difference in clinical features including HLA-B27 between patients with active and inactive MRI. Thus, BASDAI as a criterion for biologic therapy may need re-considering. Disclosure N. Jain: None. S. Byravan: None. J. Stairs: None. W. Rennie: None. M. Arumugam: Other; Speaker and Conference Fee MSD, Novartis, Abbvie.

The effect of polymorphisms in FSHR and FSHB genes on ovarian response: a prospective multicenter multinational study in Europe and Asia.

Does the presence of single nucleotide polymorphisms (SNPs) in the FSH receptor gene (FSHR) and/or FSH beta subunit-encoding gene (FSHB) influence ovarian response in predicted normal responders treated with rFSH? The presence of FSHR SNPs (rs6165, rs6166, rs1394205) has a statistically significant impact in ovarian response, although this effect is of minimal clinical relevance in predicted normal responders treated with a fixed dose of 150 IU rFSH. Ovarian reserve markers have been a breakthrough in response prediction following ovarian stimulation. However, a significant percentage of patients show a disproportionate lower ovarian response, as compared with their actual ovarian reserve. Studies on pharmacogenetics have demonstrated a relationship between FSHR or FSHB genotyping and drug response, suggesting a potential effect of individual genetic variability on ovarian stimulation. However, evidence from these studies is inconsistent, due to the inclusion of patients with variable ovarian reserve, use of different starting gonadotropin doses, and allowance for dose adjustments during treatment. This highlights the necessity of a well-controlled prospective study in a homogenous population treated with the same fixed protocol. We conducted a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium, and Spain (168 from Europe and 200 from Asia), from November 2016 until June 2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonist protocol with a fixed daily dose of 150 IU rFSH until triggering. Blood sampling and DNA extraction was performed prior to oocyte retrieval, followed by genotyping of four SNPs from FSHR (rs6165, rs6166, rs1394205) and FSHB (rs10835638). Eligible were predicted normal responder women <38 years old undergoing their first or second ovarian stimulation cycle. Laboratory staff and clinicians were blinded to the clinical results and genotyping, respectively. The prevalence of hypo-responders, the number of oocytes retrieved, the follicular output rate (FORT), and the follicle to oocyte index (FOI) were compared between different FSHR and FSHB SNPs genotypes. The prevalence of derived allele homozygous SNPs in the FSHR was rs6166 (genotype G/G) 15.8%, rs6165 (genotype G/G) 34.8%, and rs1394205 (genotype A/A) 14.1%, with significant differences between Caucasian and Asian women (P < 0.001). FSHB variant rs10835638 (c.-211 G>T) was very rare (0.5%). Genetic model analysis revealed that the presence of the G allele in FSHR variant rs6166 resulted in less oocytes retrieved when compared to the AA genotype (13.54 ± 0.46 vs 14.81 ± 0.61, estimated mean difference (EMD) -1.47 (95% CI -2.82 to -0.11)). In FSHR variant rs1394205, a significantly lower number of oocytes was retrieved in patients with an A allele when compared to G/G (13.33 ± 0.41 vs 15.06 ± 0.68, EMD -1.69 (95% CI -3.06 to -0.31)). A significantly higher prevalence of hypo-responders was found in patients with the genotype A/G for FSHR variant rs6166 (55.9%, n = 57) when compared to A/A (28.4%, n = 29), ORadj 1.87 (95% CI 1.08-3.24). No significant differences were found regarding the FORT across the genotypes for FSHR variants rs6166, rs6165, or rs1394205. Regarding the FOI, the presence of the G allele for FSHR variant rs6166 resulted in a lower FOI when compared to the A/A genotype, EMD -13.47 (95% CI -22.69 to -4.24). Regarding FSHR variant rs6165, a lower FOI was reported for genotype A/G (79.75 ± 3.35) when compared to genotype A/A (92.08 ± 6.23), EMD -13.81 (95% CI -25.41 to -2.21). The study was performed in relatively young women with normal ovarian reserve to eliminate biases related to age-related fertility decline; thus, caution is needed when extrapolating results to older populations. In addition, no analysis was performed for FSHB variant rs10835638 due to the very low prevalence of the genotype T/T (n = 2). Based on our results, genotyping FSHR SNPs rs6165, rs6166, rs1394205, and FSHB SNP rs10835638 prior to initiating an ovarian stimulation with rFSH in predicted normal responders should not be recommended, taking into account the minimal clinical impact of such information in this population. Future research may focus on other populations and other genes related to folliculogenesis or steroidogenesis. This study was supported by an unrestricted grant by Merck Sharp & Dohme (MSD). N.P.P. reports grants and/or personal fees from MSD, Merck Serono, Roche Diagnostics, Ferring International, Besins Healthcare, Gedeon Richter, Theramex, and Institut Biochimique SA (IBSA). N.L.V. and M.T.H. report consultancy and conference fees from Merck, Ferring, and MSD, outside the submitted work. P.D. has received honoraria for lecturing and/or research grants from MSD, Ferring International, and Merck. D.S. reports grants and/or personal fees from MSD, Ferring International, Merck Serono, Cook, and Gedeon Richter. A.R.N., B.A.M., C.S., J.M., L.H.L., P.Q.M.M., H.T., and S.G. report no conflict of interests. NCT03007043.

NIGERIA’S LOW CONTRIBUTION TO RECOGNIZED WORLD RESEARCH LITERATURE: CAUSES AND REMEDIES

ABSTRACT We present a first-time study on identifying the causes and remedies to Nigeria’s low contribution to globally recognized research literature. A mixed research approach involving 300 academic staff from several areas of specialization in southern Nigeria was adopted, using structured questionnaire and semi-structured interview schedule. Data obtained were analyzed using descriptive statistics and thematic technique. Furthermore, 43.7%, 28.6%, and 27.7% of the respondents were from the university, polytechnic, and college of education system, respectively. While 78.4% of the respondents agreed that the high cost of open access publication in top journals influenced Nigeria’s low contribution to research literature, over 75% reported that the low contribution was due to high cost of attending international conferences. Other factors identified were stringent conditions for paper acceptance (89.7%), scarcity of relevant information about Africa (85.4%), and paucity of high-impact journals in the libraries of Nigerian tertiary institutions (6.7%). Others were poor funding, non-usage of research findings by policymakers, lack of adequate facilities, and high penchant for publication in predatory journals, informed by promotion criteria not supportive of quality. Participants advocated for increased funding, reduced conference fees, and entrenchment of collaboration between reputable publishers abroad and African publishers.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

Developing a core outcome set for future infertility research: an international consensus development study† ‡.

STUDY QUESTIONCan a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed?SUMMARY ANSWERA minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility.WHAT IS KNOWN ALREADYComplex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret.STUDY DESIGN, SIZE, DURATIONA three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries).PARTICIPANTS/MATERIALS, SETTING, METHODSHealthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods.MAIN RESULTS AND THE ROLE OF CHANCEThe core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable.LIMITATIONS, REASONS FOR CAUTIONWe used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold.WIDER IMPLICATIONS OF THE FINDINGSEmbedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.STUDY FUNDING/COMPETING INTEREST(S)This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form.TRIAL REGISTRATION NUMBERCore Outcome Measures in Effectiveness Trials Initiative: 1023.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study† ‡.

STUDY QUESTIONCan consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting?SUMMARY ANSWERConsensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed.WHAT IS KNOWN ALREADYDifferent definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development.STUDY DESIGN, SIZE, DURATIONPotential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process.PARTICIPANTS/MATERIALS, SETTING, METHODSHealthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods.MAIN RESULTS AND THE ROLE OF CHANCEForty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting.LIMITATIONS, REASONS FOR CAUTIONWe used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries.WIDER IMPLICATIONS OF THE FINDINGSA minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set.STUDY FUNDING/COMPETING INTEREST(S)This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form.TRIAL REGISTRATION NUMBERCore Outcome Measures in Effectiveness Trials Initiative: 1023.

Neuropathy with IgM Gammopathy: Incidence, Characteristics and Management, a Rory Morrison W.M.U.K Registry Analysis

Neuropathy with IgM Gammopathy: Incidence, Characteristics and Management, a Rory Morrison W.M.U.K Registry Analysis

Dabrafenib Is a Safe and Effective Therapy in Relapsed/Refractory Classical Hairy Cell Leukemia

BACKGROUND: Hairy cell leukemia (HCL) is a rare indolent B-cell lymphoproliferative disorder. The BRAF V600E mutation was shown to be the underlying genetic driver for the vast majority of classical HCL (HCLc) cases and treatment with the BRAF inhibitor (BRAFi), vemurafenib, has proven extremely successful. Dabrafenib is an oral BRAFi used in melanoma, often in conjunction with trametinib, a MEK inhibitor. Data exists on the use of dabrafenib combined with trametinib in HCLc but there is no efficacy or safety data on either single agent dabrafenib or dabrafenib combined with rituximab. We present a small series of 7 patients treated with either single agent dabrafenib or combination dabrafenib and rituximab. METHODS: Since 2018 dabrafenib was accessible via a Novartis managed access programme for BRAF V600E mutated HCLc patients who had no alternative treatment options. Six patients received dabrafenib, 2 as single agent due to recent prior ineffective rituximab therapy or severe rituximab infusion reaction and the remaining 4 patients with dabrafenib and rituximab. Dabrafenib was given at 150mg twice daily on a continuous 28 day cycle. Rituximab 375mg/m2 IV was given once every 2 weeks for a total of 8 doses. As there was no availability for re-treatment on cessation of therapy and no other suitable/accessible treatment options, patients with ongoing response and good tolerance were continued on indefinite therapy. One additional patient was treated with frontline dabrafenib and rituximab due to various comorbidities including end stage renal failure limiting other treatment options. RESULTS: Mean age on commencing dabrafenib was 73 (52-87) and in the relapsed patients the median number of prior lines of therapy was 5 (3-13). Four patients had undergone prior splenectomy. Two patients had received prior BRAFi therapy with vemurafenib and 3 had received prior Moxetumomab. Patients received a median of 8 cycles of dabrafenib. 4 patients received all 8 cycles of rituximab with 1 discontinuing rituximab due to adverse drug reaction. Adverse drug reactions to dabrafenib were mostly grade 1-2. The most common reaction was benign keratotic skin lesions occurring in 5/7 patients. Their onset was typically after 4 weeks of treatment, persisting whilst therapy continued. Other notable adverse drug reactions were hair thinning and palmar-plantar erythrodysesthesia both occurring in 3/7 patients. Hair thinning did seem to improve with decreasing the dosage and resolve on cessation of the drug. Palmar-plantar erythrodysesthesia was managed with dose reduction and non-steroidal anti-inflammatory drugs. Response assessment criteria used were from the 2017 hairy cell leukemia foundation consensus guidelines for the diagnosis and management of patients with HCLc. All patients responded to therapy. Hematological response was rapid, most patients achieving hematological CR after 2-3 cycles. Five patients achieved a CR, 2 were MRD+ve, 2 were MRD-ve and 1 was a radiological CR. The remaining 2 patients achieved a hematological response, 1 partial and 1 complete. Six patients had sufficient follow up for assessment with 2/6 having relapsed and 4/6 remaining in remission. Median follow up was 17 months, median DOR and median OS were not reached. The 2 patients in our cohort (patients 1 and 3) receiving prior vemurafenib each received 6 cycles, 1 achieving CR lasting 3 months, the other achieving PR lasting 11 months. Both responded rapidly to dabrafenib, one treated with dabrafenib and rituximab achieved an MRD+ve CR with DOR 21 months. The other received single agent dabrafenib and achieved a hematological response with DOR 15.2 months. Treatment response and survival are shown in table 1 and figure 1. Figures 2-7 show the hematological response at time points within the first year of therapy. DISCUSSION: In this small cohort we have shown that dabrafenib as a single agent or combined with rituximab is a safe and effective therapy in BRAF V600E mutated HCLc, even in those patients with prior time limited duration BRAFi therapy. There was no hematological toxicity noted. The main adverse drug effect was development of skin lesions however none were malignant. The only malignant lesion noted pre dated the commencement of dabrafenib. Dermatological surveillance is therefore recommended. Hematological response was rapid with significant improvement seen as early as 4 weeks from commencing therapy. Disclosures El-Sharkawi: Janssen:Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche:Other: Conference fees. OffLabel Disclosure: Use of BRAF inhibitor Dabrafenib in BRAF V600E mutation positive classical Hairy Cell Leukemia.