P016 Updated Clinical Practice Guidelines for JIA management adopting Treat to Target approach: the Egyptian College of Paediatric Rheumatology initiative

Abstract Background There is an unmet need from paediatric rheumatologists and rheumatologists, managing children with JIA, for a well formulated guidelines aiming at achieving better outcomes of their patients. To establish adequate and easily adopted guidelines in management of different variants of JIA in a relatively low resources country. Method This study was carried out to achieve an Egyptian expert consensus on a treat-to-target management strategy for Juvenile Idiopathic Arthritis using Delphi technique. The preliminary scientific committee identified a total of 17 key clinical questions according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) approach. An evidence-based, systematic, literature review was conducted to compile evidence for the benefits and harms associated with JIA treatments. The core leadership team identified researchers and clinicians with expertise in JIA management in Egypt upon which Experts were gathered from different governorates and health centres across Egypt. Delphi process was implemented (2-rounds) to reacha consensus on the management recommendations of Egyptian JIA patients. Results: An online questionnaire were sent to expert panel (n = 27), of whom 26 participated in the two rounds. At the end of round 2, a total of eighteen (18) recommendation items, categorized into 4 sections to address the main 4 JIA categories, were obtained. Agreement with the recommendations (rank 7–9) ranged from 83.2–100% (average 86.8%). Consensus was reached (i.e. ≥75% of respondents strongly agreed or agreed) on the wording of all the 18 clinical standards identified by the scientific committee. Algorithms for the management of JIA polyarthritis, oligoarthritis and systemic JIA have been suggested. Conclusion A wide and representative panel of experts established a consensus regarding the management of JIA in Egypt. The developed guidelines provide a comprehensive approach to the management of JIA for ll Egyptian healthcare professionals who are involved in its management for follow up and frequent evaluation of these guidelines.

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P063 Consensus-based recommendations for treat to target management of immunoglobulin A vasculitis

Rheumatology ◽

10.1093/rheumatology/keab722.055 ◽

2021 ◽

Vol 60 (Supplement_5) ◽

Author(s):

M H Abu-Zaid ◽

S A Tabra ◽

S Salah ◽

H Lotfy ◽

H Abdulhady ◽

...

Keyword(s):

Immunoglobulin A ◽

Scientific Committee ◽

Expert Consensus ◽

Treat To Target ◽

Small Vessel Vasculitis ◽

Iga Vasculitis ◽

Online Questionnaire ◽

Egyptian Children ◽

The Central Nervous System ◽

Target Management

Abstract Background IgAvasculitis (IgAV) is the commonest cause of vasculitis in childhood. It is characterized by small vessel vasculitis of the skin, gastrointestinal tract, kidneys, joints, and, rarely, the lungs and the central nervous system. There is paucity of international guidelines for management of IgA V. the Objective is to develop guidelines specific for Egyptian children with IgA vasculitis. Method This study was carried out to achieve an Egyptian expert consensus on a treat-to-target management strategy for IgA vasculitis using Delphi technique. The preliminary scientific committee identified a total of 16 key clinical questions according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) approach. Delphi process was implemented (2-rounds) to reach a consensus. Results An online questionnaire were sent to expert panel (n = 26) who participated in the two rounds. At the end of round 2, a total of 20 recommendation items, categorized into 2 sections were obtained. Agreement with the recommendations (rank 7–9) ranged from 91.7–100%. Consensus was reached (i.e. ≥75% of respondents strongly agreed or agreed) on the wording of all the 20 clinical standards identified by the scientific committee. Algorithms for the management have been suggested. Conclusion This was an expert, consensus recommendations for the diagnosis and treatment of IgA V and IgA V nephritis, based on best available evidence and expert opinion.

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SAT0501 EARLY START OF BIOLOGICAL TREATMENT IN JUVENILE IDIOPHATIC ARTHRITIS: DOES A THERAPEUTIC WINDOW EXIST IN REAL LIFE?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4611 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1207.2-1207

Author(s):

A. García Fernández ◽

A. Briones-Figueroa ◽

L. Calvo Sanz ◽

Á. Andreu-Suárez ◽

J. Bachiller-Corral ◽

...

Keyword(s):

Disease Activity ◽

Biological Treatment ◽

Real Life ◽

Therapeutic Window ◽

Systemic Jia ◽

Active Arthritis ◽

The Impact ◽

Active Patients ◽

Active Disease

Background:Biological therapy (BT) has changed the treatment and perspectives of JIA patients but little is known about when is the best moment to start BT and the impact of this prompt iniciation.Objectives:To analyze the response to BT of Juvenile Idiophatic Arthritis (JIA) patients according to the time when the BT was started.Methods:A retrospective, descriptive study was conducted on JIA patients followed up in a referal hospital that started BT up to 24 months after diagnosis from 2000 to 2018. Disease activity was measured, at 2 years after diagnosis, according to Wallace criteria for remission (absence of: active arthritis, active uveitis, fever, rash or any other manifestation attributable to JIA, normal CRP and ESR, PGA indicating no active disease) for at least 6 months.Results:55 JIA patients that started BT up to 24 months from diagnosis were analyzed. 69,1% were girls with a median age at diagnosis of 8 years old IQR(3-13), median age at the start of BT of 9 years old IQR(3-13). Regarding JIA categories: 25,5% were Oligoarticular Persistent (OligP), 18,2% Systemic JIA (sJIA), 16,4% Entesitis related Arthritis (ERA), 12,7% Psoriatic Arthritis (APso) and Polyarticular RF- (PolyRF-), 5,5% Oligoarticular Extended (OligE) and Polyarticular RF+ (PolyRF+), 3,6% Undifferentiated (Und). 20% of patients had uveitis during followup. Conventional DMARD (cDMARD) was indicated in 83,6% of patients (95,7% Methotrexate) at diagnosis [median 0 months IQR(0-2,3)]. At the end of followup (2 years) only 30,9% of patients continued with cDMARDs. The main causes of discontinuation were: adverse events (46,7%), remission (36,7%). TNF inhibitors were precribed in 81,8% of patients and 18,2% of patients recieved two BT during the first 2 years from diagnosis. 54,5% of BT were indicated during the first 6 months from diagnosis, 27,3% from 7 to 12 months, 12,7% from 13 to 18 months, 5,5% from 19 to 24 months.After 2 years from diagnosis, 78,2% of patients were on remission and 21,8% active. Among patients with active disease: 75% had arthritis, 16,7% had uveitis and 8,3% had both. There were no differences regarding disease activity among patients with uveitis and neither taking cDMARDs. Regarding JIA categories: 66,7% of OligE, 57,1% of PolyRF- and 57,1% of APso patients were active at 2 years from diagnosis when compared to the other categories (p=0.004).Patients on remission at 24 months from diagnosis started sooner the BT than active patients [CI 95% (0,46-8,29) p=0,029]. The time when the BT was started was correlated to the activity at 2 years (K= 0,294 p=0,029). When the BT was prescribed after 7,5months from diagnosis it was correlated, in a COR curve, with a higher probability of active disease at 2 years (S= 0,67 E= 0,63). There was a correlation, among patients on remission at 2 years, between prompt start of BT and less time to reach remission (K= -0,345 p=0,024). Patients with active disease at 2 years, regardless of moment of BT iniciation, required more BT during follow-up (p=0,002).Conclusion:Prompt iniciation of BT was correlated with a better outcome. JIA patients that started BT early after diagnosis had a higher probability of remission after 2 years. Starting BT after 7,5 months was correlated with a higher probability of active disease at 2 years. Active disease at 24 months was correlated with persistent active disease during follow-up.Disclosure of Interests:None declared

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MTX optimization or adding bDMARD equally improve disease activity in rheumatoid arthritis: results from the prospective study STRATEGE

Rheumatology ◽

10.1093/rheumatology/keab274 ◽

2021 ◽

Author(s):

Cécile Gaujoux-Viala ◽

Christophe Hudry ◽

Elena Zinovieva ◽

Hélène Herman-Demars ◽

René-Marc Flipo

Keyword(s):

Disease Activity ◽

Biological Treatment ◽

Current Practice ◽

Treatment Strategies ◽

Route Optimization ◽

Treat To Target ◽

Inadequate Response ◽

Inclusion Criteria ◽

Treatment Optimization

Abstract Objectives The STRATEGE study aimed to describe treatment strategies in current practice in RA bDMARD-naive patients with an inadequate response to MTX therapy, and to compare clinical efficacy of the different therapeutic strategies on disease activity after six months. Methods Main inclusion criteria of this prospective, observational, multicentre study were confirmed RA diagnosis, treatment by MTX monotherapy, and need for therapeutic management modification. Results The 722 patients included had a mean (S.D.) RA duration of 5.3 (6.7) years, a mean DAS28 of 4.0 (±1.1); they were all receiving MTX monotherapy, 68% oral, at a mean dose of 15.0 (4.1) mg/wk. Two major strategies were identified: (i) MTX monotherapy dose and/or route optimization (72%) and (ii) bDMARD initiation ± MTX (16%). MTX dosing was modified for 70% of patients, maintained (dose and route) for 28% of patients, and interrupted for 2%. bDMARDs were started when the MTX mean dose was 17.4 mg/wk, 56% parenterally; MTX was maintained concomitantly for 96% of patients. Six-month follow-up results adjusted by propensity score showed that both options were equally successful in improving disease activity and physical function, with 63% and 68% of good-to-moderate EULAR responses, respectively. Conclusion The STRATEGE study shows the importance of initial MTX treatment optimization before initiation of a biological treatment and emphasizes the importance of treat-to-target strategy.

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Serum biomarkers confirming stable remission in inflammatory bowel disease

Scientific Reports ◽

10.1038/s41598-021-86251-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Christoph Kessel ◽

Miha Lavric ◽

Toni Weinhage ◽

Markus Brueckner ◽

Sytze de Roock ◽

...

Keyword(s):

Disease Control ◽

Serum Biomarkers ◽

Treat To Target ◽

Optimal Management ◽

Tight Control ◽

Follow Up Study ◽

Number Of Patients ◽

Bowel Diseases ◽

Inflammatory Bowel

AbstractCrohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for the confirmation of disease remission in patients with IBD. We retrospectively analyzed samples of 40 IBD patients (30 UC, 10 CD) enrolled in a tight-control follow-up study. Half of the patients had a flare during follow up. Serum was analyzed for S100A12 as well as S100A8/A9 and for 50 further biomarkers in a bead-based multiplex assay. The concentrations of 9 cytokines/chemokines and S100A8/A9 significantly differed in IBD patients with unstable remission (before flares) when compared to IBD patients with stable remission. Although the number of patients was small, ROC curve analyses revealed a number of biomarkers (IL-1β, IL-1RA, IL-8, IL13, IL-15, IL-21, IL-25, IFN-β, CXCL9, CXCL10, CXCL11, Galectin-1, G-CSF and S100A8/A9) that were elevated in patients with later occurring relapses. While earlier studies on peripheral biomarkers in IBD are limited to only few analytes, our study using a broad screening approach identified serum biomarkers with the potential to indicate unstable disease control in IBD, which may help to steer individual therapies to maintain remission.

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AB0546 5 YEARS FOLLOW-UP OF PSORIATIC ARTHRITIS PATIENTS TREATED ACCORDING TREAT-TO-TARGET STRATEGY. PRELIMINARY RESULTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1985 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1306.1-1306

Author(s):

P. Tremaskina ◽

E. Loginova ◽

T. Korotaeva ◽

S. Glukhova ◽

A. Lila

Keyword(s):

Psoriatic Arthritis ◽

Disease Activity ◽

Standard Care ◽

Early Stage ◽

Treat To Target ◽

Moderate Activity ◽

Long Term Outcomes ◽

Mean Values

Background:The concept of treat to target (T2T) in psoriatic arthritis (PsA) has been established recently and already shown its benefits [1]. But the long-term outcomes of the T2T have not been studied yet.Objectives:To study 5 years (yrs) follow-up of PsA patients (pts) treated according to T2T strategy at the early stage.Methods:35 (M/F–17/18) PsA pts fulfilling CASPAR criteria, who were treated according to T2T strategy at the early stage (PsA duration≤2 yrs) within 24 months (mos) were analyzed. At the time of evaluation mean age is 42.7±11.2 yrs, median (Me) PsA duration 72 [60;95] mos, psoriasis duration 120 [88;180] mos. All pts underwent standard clinical examinations of PsA before started T2T therapy and at follow-up. Within 24 mos of T2T strategy all pts were taking Methotrexate (MTX) monotherapy in increasing dose up to 25 mg/wk and 18 out of 35 (51%) pts received MTX in combination with iTNF. When T2T study was stopped all pts were treated according to standard care with NSAIDs, bDMARDs, MTX, tsDMARDs based on PsA activity and physician decision. The number of pts achieved minimal disease activity (MDA, 5 of 7) and remission by DAPSA (≤4)/low disease activity (LDA)≤14) at the 24 mos of T2T strategy and at 5 yrs follow-up were calculated. The results are presented in the form of mean values, median, upper and lower quartiles.Results:Me duration of follow-up is 68 [53.5;81.5] mos. At 24 mos Me DAPSA 3.48 [0.45;21.76], remission by DAPSA (REM-DAPSA) were seen in 20 out of 35 (57%) pts, LDA-DAPSA in 4 (12%) pts, moderate activity (MoA) by DAPSA in 6 (17%) pts and high disease activity by DAPSA (HDA-DAPSA) in 5 (14%) pts. MDA was noted in 21 out of 35 (60%) pts. At 5 yrs Me DAPSA 7.4 [2.22;13.87], REM-DAPSA was noted in 12 (34%) pts, LDA-DAPSA in 14 (40%), MoA-DAPSA in 5 (14%), HDA-DAPSA in 4 (12%) pts. MDA was observed in 17 of 35 pts (49%). Among 20 pts who had REM-DAPSA at 24 mos only 6 pts (30%) remained in remission at 5 yrs follow-up and 12 out of 21 pts (57.14%) remained in MDA status.Conclusion:In early PsA pts remission and MDA are achievable goal of T2T strategy. But most pts lost remission/MDA after this strategy was changed to a standard care, despite being in remission/MDA status before change of therapy. Further investigations of the long-term outcomes of T2T strategy in PsA, including radiographic outcomes are needed.References:[1]Coates LC, Moverley AR, McParland L, et al. Lancet 2015; 386: 2489–98.Disclosure of Interests:None declared.

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Defining key questions for clinical practice guidelines: a novel approach for developing clinically relevant questions

Health Research Policy and Systems ◽

10.1186/s12961-020-00628-3 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Samantha Chakraborty ◽

Bianca Brijnath ◽

Jacinta Dermentzis ◽

Danielle Mazza

Keyword(s):

Qualitative Research ◽

Clinical Practice ◽

Clinical Practice Guidelines ◽

Practice Guidelines ◽

Best Practice ◽

International Guideline ◽

Novel Approach ◽

Clinical Questions ◽

Key Questions

Abstract Background There is no standardised protocol for developing clinically relevant guideline questions. We aimed to create such a protocol and to apply it to developing a new guideline. Methods We reviewed international guideline manuals and, through consensus, combined steps for developing clinical questions to produce a best-practice protocol that incorporated qualitative research. The protocol was applied to develop clinical questions for a guideline for general practitioners. Results A best-practice protocol incorporating qualitative research was created. Using the protocol, we developed 10 clinical questions that spanned diagnosis, management and follow-up. Conclusions Guideline developers can apply this protocol to develop clinically relevant guideline questions.

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Impact of COVID-19 on management of urogynaecology patients: a rapid review of the literature

International Urogynecology Journal ◽

10.1007/s00192-021-04704-2 ◽

2021 ◽

Author(s):

Jemina Loganathan ◽

◽

Stergios K. Doumouchtsis

Keyword(s):

Evidence Synthesis ◽

Horizontal Transmission ◽

Rapid Review ◽

Review Of The Literature ◽

First Line ◽

Face To Face ◽

Manual Search ◽

Guidance Documents ◽

Management Recommendations

Abstract Introduction and hypothesis The coronavirus (COVID-19) pandemic has impacted health systems worldwide. There is a continuing need for clinicians to adapt practice to facilitate timely provision of medical care, whilst minimising horizontal transmission. Guidance and recommendations are increasingly available, and this rapid review aimed to provide a timely evidence synthesis on the current recommendations surrounding urogynaecological care. Methods We performed a literature review using PubMed/Medline, Embase and Cochrane and a manual search of national and international societies for management recommendations for urogynaecological patients during the COVID-19 pandemic. Results Nine guidance documents and 17 articles, including 10 reviews, were included. Virtual clinics are recommended for new and follow-up patients, to assess and initiate treatment, as well as triage patients who require face-to-face appointments. Outpatient investigations such as urodynamics and cystoscopy for benign indications can be deferred. Prolapse and continence surgery should be suspended, except in specific circumstances such as procidentia with upper tract complications and failed pessaries. There is no evidence to support a particular route of surgery, but recommendations are made to minimise COVID-19 transmission. Conclusions Urogynaecological patients face particular challenges owing to inherent vulnerabilities of these populations. Behavioural and medical therapies should be recommended as first line options and initiated via virtual or remote clinics, which are integral to management during the COVID-19 pandemic. Expanding the availability and accessibility of technology will be increasingly required. The majority of outpatient and inpatient procedures can be deferred, but the longer-term effects of such practices are unclear.

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Exploring the Relationships Between Resilience and News Monitoring with COVID Distress in Health Profession Students

Academic Psychiatry ◽

10.1007/s40596-021-01444-9 ◽

2021 ◽

Author(s):

Allison Yu ◽

Michael Wilkes ◽

Ana-Maria Iosif ◽

Margaret Rea ◽

Alice Fisher ◽

...

Keyword(s):

Health Science ◽

Health Profession ◽

First Year ◽

Linear Regression Models ◽

Online Questionnaire ◽

Student Stress ◽

School Of Nursing ◽

Resilience Scale ◽

Related Stress

Abstract Objective Alarming rates of anxiety and burnout in pre-clinical health profession trainees are now challenged by additional COVID-19 stressors. This study explored COVID-related stressors among first-year medical, physician assistant, nurse practitioner, and veterinary medical students. The authors examined associations between resilience, news monitoring, and COVID stress. Methods Students completed an online questionnaire that included the Brief Resilience Scale at their matriculation in August 2019. Survey results were linked to demographic information collected by all schools. A follow-up survey in May 2020 included original questions on COVID-19 stressors and news monitoring. Statistical analyses included descriptive statistics and multivariable linear regression models. Results Across schools, 74% (266/360) provided consent for the 2019 survey, and 76% (201/264) responded to COVID-19 questions in the follow-up 2020 survey. Students were “extremely” or “very” concerned about family members getting infected (n = 71, 76% School of Medicine (SOM); n = 31, 76% School of Nursing (SON); n = 50, 75% School of Veterinary Medicine (SVM)) and curriculum schedule changes (n = 72, 78%, SOM; n = 28, 68% SON; n = 52, 79% SVM). Greater frequency of COVID news monitoring was associated with greater COVID-related stress (p = 0.02). Higher resilience at matriculation was associated with lower COVID-related stress ten months later (p < 0.001). Conclusions Amid COVID-19 uncertainty, health science schools should address the immense student stress regarding curriculum disruptions. The results of this study underscore the powerful role of resilience in protecting against stress not only during the known academic rigor of health professions training but also during unprecedented crises.

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Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8029 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8029-8029

Author(s):

Binod Dhakal ◽

Shruti Sharma ◽

Svetlana Shchegrova ◽

Minu Maninder ◽

Meenakshi Malhotra ◽

...

Keyword(s):

Bone Marrow ◽

Residual Disease ◽

Prognostic Significance ◽

Unmet Need ◽

Progression Free Survival ◽

Multiparameter Flow Cytometry ◽

High Dose ◽

Blood Samples ◽

Ctdna Analysis

8029 Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), MM patients invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker. Currently, MRD in MM is monitored via bone marrow aspirate sampling. Marrow MRD assays are limited by the spatial heterogeneity of marrow MM localization; extramedullary disease and sampling variability of marrow aspiration. Sensitive, non-invasive blood-based MRD assay is an unmet need. ctDNA as a noninvasive biomarker can be utilized to predict relapse in MM. Here we attempt to evaluate MRD using ctDNA in AHCT recipients with MM. Methods: In this retrospective, single-center study, we analyzed ctDNA MRD in blood samples collected from 28 patients with MM after upfront AHCT. A total of 80 plasma timepoints were available pre and post AHCT with a median follow-up of 92.4 months. Multiparameter flow cytometry (MFC) at 10-4 level was used to assess the MRD from the BM biopsy. Individual bone marrow aspirates or FFPE slides from the time of MM diagnosis and matched normal blood were whole-exome sequenced, and somatic mutations were identified. MRD assessment at 3 months post-AHCT was performed by ctDNA analysis using a personalized, tumor-informed (SignateraTM, bespoke mPCR NGS assay). The prognostic value of ctDNA was evaluated by correlating MRD status with clinical outcomes. Results: Table provides the baseline disease characteristics. Median age was 67 [41-75] years and 16 [57.1%] were males. ctDNA was detectable in 70.8% (17/24) of pre-AHCT, 53.6% (15/28) of ̃3 months post-AHCT, and 39.2% (11/28) of patients during the surveillance phase post-AHCT. Of the 15 ctDNA MRD positive patients, 93.3% (n=14) experienced relapse on follow-up (hazard ratio: 5.64; 95% CI: 1.8-17; p=0.0003). Patients negative for ctDNA at 3 months post-AHCT had significantly superior progression-free survival (PFS) compared to positive (median PFS, 84 months vs. 31 months; p=0.003) The positive predictive value (PPV) for relapse among patients positive for ctDNA at 3 months post-AHCT was 93.3%, and significantly higher than marrow MFC of 68.4%. Conclusions: Our study shows the feasibility that a tumor-informed assay on archival blood samples is predictive of relapse post-AHCT. Future prospective studies with real-time marrow NGS and ctDNA samples are needed to define the role of ctDNA in MM and its prognostic significance.[Table: see text]

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Evolving Unmet Need in Patients Refractory to Lenalidomide: Overview of the Clinical Trials in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2020-142642 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Maria-Victoria Mateos ◽

Rohan Medhekar ◽

Istvan Majer ◽

Mehmet Turgut

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Literature Review ◽

Board Of Directors ◽

Unmet Need ◽

Publicly Traded ◽

First Line ◽

Advisory Committees ◽

Line Of Therapy

Introduction: The majority of newly diagnosed multiple myeloma (NDMM) patients are currently treated with lenalidomide-based regimens as their first line of therapy. This trend is likely to continue in the coming years. Typically, lenalidomide is administered until disease progression and has significantly contributed to better outcomes in these patients. However, most patients relapse, and prognosis worsens with each relapse. The choice of optimal treatment for patients who relapse while receiving lenalidomide as first line of therapy is unclear. Moreau et al (Blood Cancer J. 9, 38 [2019]) concluded that there is limited data on approved combinations for treating these patients and are restricted by the low number of lenalidomide-refractory patients enrolled in the pivotal trials. Results from the ongoing clinical trials of the combination of carfilzomib and anti-CD38 antibodies were not available at the time of the Moreau et al publication. The aim of this targeted literature review was to include this new data and to summarize currently available evidence on progression-free survival (PFS) for the treatment of RRMM patients who progressed on lenalidomide-based regimens. Methods: A targeted literature review was conducted to identify registrational clinical trials in patients with RRMM reporting PFS outcomes. PubMed, congress proceedings, and product labels were searched between Jan 2014 to July 2020. In addition to PFS, demographic, disease characteristics and treatment history were extracted for the trial populations to contextualize potential variations in study outcomes. The regimens studied in these trials were classified as lenalidomide-based, proteasome inhibitor (PI)-based and pomalidomide-based. Number of prior lines of therapy, prior exposure and refractoriness to lenalidomide and bortezomib were reported. Results: Twelve registrational trials were identified based on the search criteria (Table 1). Most pivotal trials assessing lenalidomide-based regimens (POLLUX, ELOQUENT-II, TOURMALINE-MM1) except the ASPIRE trial excluded patients who were refractory to lenalidomide. Trials evaluating PI-based regimens (e.g., CANDOR) or pomalidomide-based regimens (e.g., OPTIMISMM) included these patients, with more recent studies enrolling a larger proportion. Percentage of lenalidomide-exposed (and lenalidomide refractory) ranged from 40% (32%) in CANDOR to 98% (90%) in ELOQUENT III. These studies also enrolled a larger proportion of patients who were bortezomib-exposed, although most of these patients were at first relapse, with the exception of ELOQUENT III and ICARIA where most patients were at third relapse. Among lenalidomide-refractory patients, the median-PFS (mPFS) observed for the pomalidomide-based regimens ranged from 9.5 to 10.1 months and that observed for PI-based regimens ranged from 4.9 to 25.7 months. PFS in the lenalidomide-refractory subgroup was considerably shorter than in the ITT population. The mPFS for patients receiving carfilzomib/daratumumab/dexamethasone (KDd; CANDOR) and isatuximab/carfilzomib/dexamethasone (IsaKd; IKEMA) was not reached at median follow-up of 16.9 and 20.7 months respectively. While the mPFS for (KDd) for lenalidomide-refractory patients in CANDOR trial was not yet reached at median follow up of 16.9 months; the mPFS of 25.7 months for KDd in the MMY-1001 trial appears to be the longest among the assessed regimens. Conclusion: Patients refractory to lenalidomide have shorter PFS and represent a population with high unmet need. This targeted literature review suggests that the PI-based KDd regimen provides longer PFS compared to other lenalidomide-sparing regimens in lenalidomide-refractory populations. Heterogeneity across trial populations may limit the comparability of these treatments. Disclosures Mateos: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; GlaxoSmithKline: Consultancy. Medhekar:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Majer:Amgen (Europe) GmbH: Current Employment, Current equity holder in publicly-traded company.

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