ABSTRACT:Idecabtagene vicleucel (ide-cel), an adoptive chimeric antigen receptor T-cell therapy directed against B-cell maturation antigen (BCMA), has demonstrated high response rates and improved survival in patients with relapsed/refractory multiple myeloma. However, all patients eventually relapse, and data on salvage therapy outcomes remain limited. We conducted a national, real-world study of 154 patients relapsing after ide-cel, with a median time to progression of 6.0 months (interquartile range, 3.0-9.9). Salvage therapies included anti-BCMA bispecific antibodies (BsAbs) (n = 79), non-BCMA BsAbs targeting GPRC5D or FcRH5 (n = 12), combinations of immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody (n = 40), and others (n = 23). Median overall survival (OS) was 12.12 months (95% confidence interval, 6.6 to not reached), and median progression-free survival (PFS) was 3.48 months (95% CI, 2.6-6.37). The overall response rate (≥ partial response) was higher in patients treated with BsAbs (36%) than others (13%, P = .002). Treatment with non-BCMA BsAbs resulted in significantly higher ORR (67% vs 30%, P = .018), OS (19.48 vs 8.41 months, P = .034) and PFS (9.2 vs 3.81 months, P = .035) compared to anti-BCMA BsAbs. Early relapse after ide-cel (≤6 months) was associated with worse outcomes (OS: 5.95 vs 12.58 months, P = .040), as was extramedullary disease (OS: 13.8 vs 6.28 months, P = .033) and exposure to >3 prior lines of therapy. In summary, anti-BCMA BsAbs offered limited efficacy whereas non-BCMA BsAbs may offer a promising therapeutic approach following ide-cel early relapse. These results underscore the potential benefits of diversifying targets in relapse post-ide-cel treatment strategies. This trial was registered at www.clinicaltrials.gov as #NCT04328298.

Introduction: Randomized clinical trials in acute leukemia often involve post-randomization allogeneic stem cell transplantation (alloSCT), an intercurrent event that can affect the treatment effect being estimated. The estimand framework, introduced in regulatory guidance on clinical trial methodology, was developed to clarify the scientific question of interest and to define strategies for handling intercurrent events. This study aimed to quantify the bias induced by right-censoring at alloSCT when estimating a hypothetical treatment effect and to evaluate inverse probability of censoring weighting (IPCW) as an alternative.Methods: Simulations of two-arm RCTs were conducted with a binary prognostic covariate affecting both the risk of clinical events and the probability of alloSCT. Time-to-event outcomes and alloSCT times were generated using cause-specific exponential hazard models. The true hypothetical treatment effect was computed from a large reference population to obtain population-averaged effects. Two approaches were compared: right-censoring at alloSCT and IPCW. Bias was assessed using mean relative bias, under multiple scenarios with varying treatment and prognostic effects on both the outcome and alloSCT. Results: Right-censoring yielded unbiased estimates only when the prognostic covariate did not affect the clinical event or when the treatment had no effect on the probability of alloSCT. In realistic scenarios where alloSCT depended on prognosis and treatment effect, censoring induced substantial relative bias (up to 10%), with magnitude and direction varying with treatment and covariate effects. IPCW substantially reduced bias across scenarios. Discussion: Right-censoring at alloSCT does not reliably estimate hypothetical treatment effects in acute leukemia trials. IPCW provides a conceptually appropriate causal alternative but requires careful model specification and sensitivity analyses. Explicit definition of estimands, alignment of statistical methods with the clinical question, and transparent reporting are essential to ensure valid, interpretable, and clinically meaningful conclusions.

Septic shock in cancer patients remains associated with a grim prognosis. With regard to the high prevalence of anemia, the optimal hemoglobin target to restore tissue oxygenation remains uncertain. This was a multicenter superiority randomized controlled trial carried out in 18 centers in France. Adult patients with hematological or solid malignancies presenting with septic shock with lactate level > 2.0 mmol/L and hemoglobin level < 9.0 g/dL were randomly assigned to liberal or restrictive red blood cell (RBC) transfusion directed by hemoglobin thresholds of 9.0 g/dL or 7.0 g/dL during the first 48 h of resuscitation. The primary endpoint was 12-h lactate reduction, defined as normalization ≤ 2.0 mmol/L or relative decrease by 30

Crohn’s disease (CD) often leads to progressive bowel damage and disability. Disability has been proposed as an endpoint for disease-modification trials despite lack of data on its evolution. We described the evolution of disability within the first two years in a cohort of newly diagnosed CD. The Crohn’s Disease Cohort (CROCO) is an international, prospective, multicenter study (19 centers), in which enrollment is complete but follow-up is ongoing. It includes patients with newly diagnosed CD (within 12 months of diagnosis) and evaluates the progression of bowel damage and disability. Disability was measured using the validated Inflammatory Bowel Disease Disability Index (IBD-DI), which includes 14 questions scoring from 0-100 across domains of health, sleep and energy, emotional well-being, body image, pain, defecation, interpersonal activities, and work/education. The IBD-DI was categorized as no disability (0–20), mild disability (21–35), moderate disability (36–50), and severe disability (51–100). We assessed changes in IBD-DI scores between baseline and 24 months. Among the 539 patients enrolled in CROCO, the median time between diagnosis and inclusion was 3.7 [1.5;7.3] months. IBD-DI was available at the time of inclusion in 517 patients (median IBD-DI=21.4[10.7-37.5]). Distribution across IBD-DI categories is given in Table 1. At year 1 (multivariable analysis), female (OR = 2.08 [1.17-3.69]), patients with mild (OR = 5.23[2.52-10.86]), moderate-to severe disease per Harvey-Bradshaw Index (HBI) (OR = 8.72 [3.57-21.26] for) or with extra-intestinal manifestations (EIMs) (OR = 2.31 [1.31-4.09]) had higher IBD-DI. In 226 patients IBD-DI was available at baseline, year 1, and year 2 (Table 1). Between baseline and year 2, disability decreased in 31% of patients, remained stable in 48%, and increased in 21% (Figure 1). Changes in IBD-DI were significantly associated with sex (p = 0.003) and baseline symptoms (HBI) (p < 0.001), but not with EIMs, treatments, or surgical history. Among patients who underwent intestinal resection within the first year after diagnosis, IBD-DI decreased in 33%, remained unchanged in 44%, and increased in 22% between baseline and year 2 (p = 0.92). Initiation of advanced therapy within the first year after diagnosis had no impact on changes in IBD-DI between baseline and year 2 (p = 0.63). Disability in newly diagnosed CD patients remained highly dynamic in the first 2 years after diagnosis, with more than half of patients changing across categories, and a substantial proportion maintaining moderate-severe disability. These findings highlight a need for new strategies to better understand and promote disability improvement in early disease course. Conflict of interest: Prof. Dr. Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Dodel, Marie: No conflict of interest Revés, Joana: None Arebi, Naila: Personal Fees: Janssen,Lilly, Pfizer and Takeda Non-financial Support: Janssen (J & J), Novonesis Fadra, Adam: None to declare Madsen, Gorm Roager: No conflict of interest Burisch, Johan: Grant: Johnson & Johnson, MSD, Takeda, Tillots Pharma, BMS, Novo Nordisk Personal Fees: Celgene, MSD, Pfizer, AbbVie, Takeda, Tillots Pharma, Samsung Bioepis, BMS, Pharmacosmos, Galapagos, Zealand Pharma, Orion Pharma, Ferring, Johnson & Johnson Cravo, Marilia: No conflict of interest Kaimakliotis, John: No conflict of interest Vieujean, Sophie: No conflict of interest Van Kemseke, Catherine: No conflicts Ellul, Pierre:...................................................................................... Conti, Kelly: No conflict of interest Duricova, Dana: Personal Fees: Lecture fee from Janssen, Takeda, Pfizer, Eli Lilly, AbbVie, Ferring. Horutova, Jana: No conflict of interest Rodríguez-Lago, Iago: Financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. Supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza (Grant No 2020111061 and 2023222006). Elorza, Ainara: No conflict of interest Ordás Jiménez, Ingrid: I have received financial support for travel and educational activities, and have served as a speaker or advisory board member for the following companies AbbVie, MSD, Pfizer, Takeda, Janssen, Kern Pharma, Chiesi, Falk Pharma, and Faes Farma. I have also received research funding from AbbVie, Faes Farma, and Takeda. Fernandez Clotet, Agnes: None Sebastian, Shaji: No conflict of interest Thut, Jessica: No conflict of interest Mocanu, Irina: No conflict of interest Hernández Ramirez, Vicente: Vicent Hernandez has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, FAES Farma, Galapagos, Lilly and Casen-Recordati Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Pedersen, Natalia: No any Conceição, Daniel: No conflict of interest Goldiș, Adrian Eugen: No conflict of interest Guedes, Ana: No conflict of interest Ribeiro, Raquel: No conflict of interest Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Bigot, Noémie: No conflict of interest Mary, Jean-Yves: No conflict of interest Lambert, Jérôme: No conflict of interest Colombel, Jean-Frédéric: Grant: AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus and Bristol Myers Squibb Lectures from: AbbVie, Roche and Takeda Other: AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, candidrx Celgene, Celltrion, Clearview Curogen, Eli Lilly, Envision Pharma Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Roche, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi, Sun Pharma, Takeda, Teva, TiGenix, and is holding stock options in Intestinal Biotech Development Tinoco da Silva Torres, Joana: Grant: Abbvie, Janssen Personal Fees: Pfizer, Janssen, Abbvie, Sandoz, Lilly, Sanofi, Takeda Non-financial Support: Janssen, Abbvie

BACKGROUND & AIMS:Ileocolonic resection remains common in Crohn's disease (CD) despite increasing biologic use. The aim of this study was to identify risk factors for postoperative recurrence and to assess prophylactic biologic therapy effectiveness in relation to risk factors. METHODS:This prospective multicentre study included adults with CD undergoing ileocolonic resection (ICR). The primary endpoint was endoscopic recurrence (modified Rutgeerts score ≥i2b) within the year following surgery. Factors associated with endoscopic recurrence were identified using a logistic regression model. A composite time-to-event endpoint was defined for long-term follow-up based on clinical, endoscopic, and/or imaging data. An external validation of our predictive model was performed in 2 independent international cohorts. RESULTS:Among 632 patients (median disease duration, 7.8 years), 78% had prior biologic exposure; 44% received postoperative biologic prophylaxis. Endoscopic recurrence occurred in 237 patients (37.5%). In multivariable model, risk factors included: male sex (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.38-2.83), active smoking (OR, 2.37; 95% CI, 1.56-3.62), previous ICR (OR, 1.78; 95% CI, 1.13-2.82), previous exposure to 1 (OR, 2.15; 95% CI, 1.37-3.42) or more than 1 biologic (OR, 2.41; 95% CI, 1.39-4.22). Biologic prophylaxis significantly reduced recurrence risk (OR, 0.31; 95% CI, 0.20-0.45), independently of these risk factors. A predictive nomogram based on multivariable analysis achieved an area under the receiver operating characteristic curve of 0.72, with similar performance in external cohorts. Clinically significant recurrence, observed in 22.9%, 36.5%, and 53.2% at 3, 5, and 10 years, was associated with severity of early endoscopic recurrence. CONCLUSIONS:Postoperative recurrence risk can be estimated using a model based on clinical factors. Biologic prophylaxis is highly effective in preventing early endoscopic recurrence, regardless of risk profile. CLINICALTRIALS:gov, Number: NCT03458195.

Assessment of quality and safety indicators (QSIs) remains often based on time-consuming manual Electronic Health Record (EHR) review. As part of a pilot study to examine the feasibility of automating the calculation of French national QSIs using a Clinical Data Warehouse (CDW), we focused on the measure of door-to-imaging time (DTI time) in stroke management, i.e., the time interval between arrival at the hospital and the first stroke diagnostic imaging, through a retrospective observational study of patients hospitalized in the Greater Paris University Hospitals (AP-HP) for an acute stroke in 2022. We automatically computed the DTI time for more than 6,000 medical records in the CDW using a systematic approach and validated this method by matching the results against the manual AP-HP EHR review from the 2022 French national QSI audit. In this Matched population, CDW and manual EHR review methods agreed on estimating overall indicators, but showed discrepancies in the case-by-case analysis, mainly because of human variability both in EHR completion and manual reviewing. Automation looks promising in a context of limited professional resources but requires structured and validated data, interoperability in the case of inter-institutional stays, and validly measurable QSI.

Frontline high-dose therapy (HDT) is, in 2025, the standard of care for patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT). Prior to high-dose melphalan, induction therapy with quadruplet combinations is also proposed systematically when possible. Lenalidomide maintenance until progression is also recommended per international guidelines. This strategy has been developed over recent decades, based on results of phase 3 trials designed and conducted by different academic groups. With these therapeutic advances, the median overall survival (OS) for patients with MM has increased from 5 years in the 1990s, to over 15 years at present. Here, we present the contribution of the French myeloma cooperative group Intergroupe Francophone du Myélome (IFM) to these advances in the newly diagnosed transplant-eligible (NDTE) setting.

Background: The combination of different biological and targeted synthetic DMARDs (i.e., combotherapy) has recently emerged in the management of immune-mediated inflammatory diseases (IMID). However, real-life data across specialities and prognostic factors related to combotherapy are lacking. Methods: Multicenter observational study conducted using the Clinical Data Warehouse from Paris Hospitals' Public Assistance including IMID patients under combotherapy, and a matched monotherapy control group. The primary endpoint was the occurrence of serious adverse events (SAE), defined by severe infections, major cardiovascular events, neoplasia and mortality (all-cause). Results: From 42,071 subjects having an IMID, 131 combotherapy lines were identified among 125 patients (median age of 36 years, 58 % females) between 2017 and 2022. The most frequent IMIDs were inflammatory bowel disease (48.8 %), connective tissue diseases (23.2 %), inflammatory myopathies (14.4 %) and vasculitis (11.2 %). After a median follow-up of 15 months [IQR 19], 30 (24%) patients presented severe infections, 5 (4 %) neoplasia, 4 (3.2 %) venous thromboembolism, 3 (2.4 %) acute coronary syndromes and 7 (5.6 %) deaths. The 1-year cumulative incidence of SAE and severe infections were 29 % (95 %CI 21-38), and 24 % (95 %CI 16-32), respectively. The survival, incidence of SAE and severe infections were not statistically different from combotherapy patients compared to monotherapy controls (n=251) after adjustment for confounders. In multivariate analyses, we found abatacept + JAKi (HR 6.81, 95 %CI 1.88-24.68), anti-IL-1-based (HR 4.82, 95% CI 1.17-19.89) and anti-CD20-based (HR 4.03, 95 %CI 1.22-13.31) combotherapies to be independently associated with an increased risk of SAE. Conclusion: The overall risk of SAE under combotherapy does not seem greatly increased compared to monotherapy, but certain combinations warrant caution. The combotherapy composition seems predictive of safety outcomes.

9583 Background: Two hedgehog pathway inhibitors (HHIs) have been approved for the treatment of locally advanced basal cell carcinoma (laBCC): vismodegib and sonidegib. Efficacy of both seem similar, even though no head-to-head comparison has been performed. However, adverse events (AEs) in pivotal trials seemed less frequent with a later onset with sonidegib. CARADERM is a French national database created in 2013 to improve the management of rare skin tumors, including laBCC. The objective of our study was to compare the safety profile of HHIs in this real-life cohort. Methods: LaBCC patients from the CARADERM database were reviewed. Patients who started either vismodegib or sonidegib at least one year before analysis were included. Type and grade of AEs were collected when available. Cumulative incidence of the first occurrence of adverse events was estimated, with treatment discontinuation as a competing event. Results: In the total cohort of 452 laBCC patients, 330 met the inclusion criteria: 280 (85%) treated with vismodegib and 50 (15%) with sonidegib. The median follow-up was 22.3 months. Clinical characteristics (including age, gender, performance status, localization and tumor size) were similar for both groups. The cumulative incidence of the first AE was significantly lower with sonidegib (43.5%, 95% confidence interval (95%CI) = 29.0-57.2 at 12 months) than with vismodegib (63.5%, 95%CI = 57.5-68.9 at 12 months, p=0.0014) (Table 1). For vismodegib treated patients, 191 (68%) experienced at least one AE. The most frequent were cramps (n=123, 44%), dysgeusia (n=123, 44%) and alopecia (n=88, 31%). For sonidegib treated patients, 22 (44%) experienced at least one AE. The most frequent were cramps (n=8, 16%), alopecia (n=7, 14%) and dysgeusia (n=6, 12%). Major AEs seemed to be less frequent and to appear later with sonidegib, with a significant difference for cramps (p=0.007) and dysgeusia (p=0.001), but not significant for alopecia (p=0.059). Conclusions: We present here the largest real-life comparison of HHIs in a real-life cohort of laBCC patients. The cumulative incidence of the first AE was significantly lower with sonidegib. Even though the range of AEs was similar with both HHIs, dysgeusia and cramps were less frequent with sonidegib. These data highlight the difference in terms of tolerance of both HHIs, with a later onset and lower frequencies of AEs with sonidegib. However, though both groups were clinically comparable, vismodegib was overrepresented compared to current prescriptions of HHIs, and further analyses are mandatory to confirm these data. Cumulative incidence of first adverse event at 3, 6 and 12 months. 3 months [95CI] 6 months [95CI] 12 months [95CI] Sonidegib 16.3 % [7.5 ; 28.0] 26.8 % [15.2 ; 39.8] 43.5 % [29.0 ; 57.2] Vismodegib 31.6 % [26.2 ; 37.2] 55.5 % [49.5 ; 61.2] 63.5 % [57.5 ; 68.9] 95CI = 95% confidence interval.

Background:Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease that can be associated with significant bowel damage and disability. The Lémann Index (LI) is a validated tool for measuring cumulative bowel damage in CD patients through a comprehensive assessment of stricturing, penetrating and surgical lesions. However, prospective studies evaluating bowel damage progression in recently diagnosed CD patients remain limited. Objectives:To characterise the absolute and longitudinal variations in bowel damage progression, as measured by the LI, in a cohort of recently diagnosed CD patients, and to assess its association with relevant disease features, including disease phenotype, treatment strategies, biomarkers and disability. Design:Study protocol for the Crohn's Disease Cohort Study (CROCO Study), a multicentre, European, prospective cohort study. Methods and analysis:Patients with recently diagnosed CD (within the previous 12 months) will be enrolled and followed up for 5 years. Patients will receive standard-of-care treatment determined by the practising gastroenterologist. Morphological assessments to measure the LI and to evaluate bowel damage progression will be performed at years 1, 3 and 5 after the diagnosis. Disability will be assessed annually using the Inflammatory Bowel Disease - Disability Index (IBD-DI). The primary outcome will be the absolute LI at year 3 following diagnosis. Predictors of bowel damage progression and the association between bowel damage and disability will be analysed. Discussion:The CROCO study represents a unique multicentre cohort of recently diagnosed CD patients, designed to advance the understanding of CD's natural history and evolution. It will facilitate the development of composite scores for predicting bowel damage progression and provide valuable tools for designing future disease-modification trials. Trial registration:NCT05420233.

BACKGROUND/AIMS:Phase III randomized clinical trials (RCTs) aim to evaluate the benefits of a new treatment. When conducted in patients with malignancies, most RCTs use a right censored endpoint, with conclusions regarding efficacy based on the p value of the logrank test. Recently, the survival inferred fragility index (SIFI) has been proposed as a measure of the robustness of the treatment effect. Applied to real RCTs, the reported SIFI values were very low. We hypothesized that such values relied on the contamination of the trial. METHODS:We performed a simulation study of individuals enrolled in an RCT, generating survival times under several realistic scenarios differing in treatment effects, sample sizes and amount of censoring. Contamination of the sample by individuals with a very specific prognosis was studied. RESULTS:Surprisingly, under the null of no treatment effect, the standard SIFI exhibited very low values, poorly sensitive to the sample size. However, under both the null and the alternative hypotheses, the p value and the amount of censoring influenced the value. By contrast, randomly selected patients, rather than those selected at the survival tails, widely modified the results, notably with an impossibility of finding value under the null in a large proportion of cases. When contaminating the sample with individuals with very poor or good outcomes, results were close to those of the standard. CONCLUSIONS:The SIFI should not be used as a measure of robustness of survival trials, as it relates to a very specific group of individuals. At least, a random selection of patients should be used in its calculation.

7500 Background: The phase III IFM2020-02-MIDAS study (NCT04934475) evaluated a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Results from the IsaKRD induction phase have been previously published (Perrot et al., Blood, 2025). Here, we present the results from the MRD-driven consolidation phase of the trial. Methods: MIDAS is a multicenter, open-label, randomized phase 3 trial involving transplant-eligible patients aged 18-65 with NDMM. Patients achieving post-induction MRD negativity at a threshold of 10⁻⁵ by next-generation sequencing (NGS) were randomized to either 6 additional cycles of IsaKRD (Arm A) or autologous stem cell transplantation (ASCT) followed by 2 cycles of IsaKRD (Arm B), followed by lenalidomide maintenance. MRD-positive patients after induction (MRD ≥10⁻⁵) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance. Randomization was stratified by cytogenetic risk and center for both comparisons, and by MRD negativity at 10⁻⁶ post-induction for the Arm A vs. Arm B comparison. The primary endpoint was MRD negativity at 10⁻⁶ (by NGS) prior to maintenance for both comparisons. Results: A total of 485 patients with post-induction MRD negativity were randomized to Arm A (n=243) or Arm B (n=242). The pre-maintenance MRD negativity rates at 10⁻⁶ were 84% in Arm A and 86% in Arm B (Odds Ratio [OR] 1.17, 95% confidence interval [CI] 0.64–2.76, p=0.64). Additionally, 233 MRD-positive patients (10⁻⁵) were randomized to Arm C (n=109) or Arm D (n=124), with 19 patients (15%) not receiving the planned tandem ASCT. Pre-maintenance MRD negativity rates at 10⁻⁶ were 40% in Arm C and 32% in Arm D (OR 0.73, 95% CI 0.42–1.25, p=0.31). During the consolidation phase, 5 patients experienced disease progression (2 in Arm A, 0 in Arm B, 0 in Arm C, 3 in Arm D), and 2 patients died without progression in Arm A. No new safety signals were identified compared to the induction phase. The study is ongoing. With a median follow-up of 16.8 months in Arms A/B and 16.3 months in Arms C/D, sustained MRD negativity and progression-free survival (PFS) data are not yet available. Conclusions: After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10⁻⁵, MRD negativity rates at 10⁻⁶ before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10 -5 , tandem ASCT did not significantly improve MRD negativity rates at 10⁻⁶ before maintenance. Further follow-up, including sustained MRD negativity and PFS data, is needed to evaluate the long-term outcomes of this MRD-adapted strategy. Clinical trial information: NCT04934475 .

BACKGROUND/AIMS:Crohn's disease (CD) progresses to structural bowel damage (SBD). The Lémann Index (LI) captures stricture extent/severity, penetrating disease and surgery as a SBD score, and is earmarked for future CD modification trials. Understanding knowledge gaps and perceived barriers is critical to wider adoption. METHODS:A multinational, cross-sectional study was distributed through a survey link (REDCap, Research Electronic Data Capture) to gastrointestinal professional societies with snowball sampling using 23 questionnaire items in 5 sections to determine SBD and LI knowledge, and LI acceptability. Factors associated with acceptability and perception were evaluated. RESULTS:Of the 107 respondents, 49 (45.8%) were female; 87 (81.3%) were from Europe. Most were inflammatory bowel disease specialists (n = 80, 74.8%) or general gastroenterologists (n = 22, 20.6%), managing > 40 CD patients per month (n = 35, 32.7%). A total of 98 (91.6%) knew about SBD; "very important" rating for clinical trials and clinical practice was 56.1% and 41.4%, respectively. A 39.3% describe LI scoring as "very difficult" or "difficult"; 33.6% reported "significant" or "a lot" of effort. Acceptability (composite scores of > 36) were significantly associated with respondents who had received LI training (P<0.001). Automated methods, intestinal ultrasound and evidence of benefit would encourage LI use in clinical trials, while additional time and automated methods would promote use in clinical practice. The top 3 perceived adoption barriers were: lack of time (60.7%), limited automated methods (47.7%) and need for dedicated radiologists (38.3%). CONCLUSIONS:Most respondents had baseline knowledge of SBD. The LI was perceived as important for advancing future CD research and care. More training and automation will facilitate LI adoption.

In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD. Between December 2021 and July 2023, 791 patients were enrolled across 72 centers. The median age was 59 years; 13% had ISS-stage III, 5% had R-ISS-stage III, and 8% had high-risk cytogenetics (IFM Linear Predictor cytogenetic score >1). Overall, 96% (N=757) of patients completed induction. The median CD34+ cell yield was 7 × 106/Kg, with 94% of patients able to proceed with a potential tandem transplant. The best overall response rate was 95%. In the intent-to-treat population, 91% achieved a very good partial response or better after induction, with MRD-negativity rates of 63% at 10-5 and 47% at 10-6. MRD-negativity rates differed across ISS stages and cytogenetic subgroups. During induction, 7 patients experienced disease progression, and 5 died due to disease progression (N=1), cardiac events (N=2), or other causes (N=2). The most common grade 3/4 adverse events were neutropenia (25%), thrombocytopenia (5%), and infections (7%); only 13% of patients reported any grade peripheral neuropathy. IsaKRD induction yielded deep responses and high MRD-negativity rates while ensuring successful stem cell collection, with no new safety signals. Continued follow-up of this ongoing study is required to confirm these findings.

Background: Locally advanced basal cell carcinoma (LaBCC) is a challenging condition. The European Association for Dermato-Oncology (EADO) suggested the classification of laBCC into 5 groups. In this study, we aimed to describe patient characteristics and treatment responses in a large cohort of real-life laBCC patients treated with systemic therapy from a nationwide French database (CARADERM). Methods: LaBCC patients from the CARADERM database were analyzed. Patient demographic data, tumor characteristics, response to treatment and reasons for discontinuation, if applicable, were retrospectively collected. We allocated every patient to the corresponding group according to the EADO classification. Results: The cohort included 452 patients (median age of 77 years and 59 % male sex). LaBCC in the critical zone was the most common group (38 %). Therapeutic response to Hedgehog inhibitors after 10 months of follow-up was evaluated in 353 patients. Complete (CR) and partial response were 39 % and 49 %. Patients with common laBCC achieved CR more frequently (47 %) than patients with very advanced BCC (29 %). Among the 55 patients who achieved CR and stopped treatment, 25 relapsed. The cumulative incidence of relapse at 18 months was 64.2 % (95 % confidence interval (95CI) = 44.6;78.4). The treatment discontinuation rate at 2 years was 88.1 % (95CI = 83.8;91.3). Sonidegib appeared more tolerable. Conclusion: In this largest ever real-life laBCC cohort, tumors were more frequently involving critical areas. The response to treatment was not significantly different between clinical groups, although patients with very advanced BCC had a lower CR rate. The overall efficacy was comparable to that of pivotal trials.