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Objective: To design a whole-body MR protocol using exclusively diffusion-weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with diffuse large B-cell lymphoma (DLBCL), with integrated FDG PET/CT as the reference standard.Methods: Fifteen patients underwent both whole-body DWI (b = 50, 400, 800 s/mm(2)) and PET/CT for pretreatment staging. Lymph node and organ involvement were evaluated by qualitative and quantitative image analysis, including measurement of the mean apparent diffusion coefficient (ADC).Results: A total of 296 lymph node regions in the 15 patients were analysed. Based on International Working Group size criteria alone, DWI findings matched PET/CT findings in 277 regions (94%) (kappa score = 0.85, P < 0.0001), yielding sensitivity and specificity for DWI lymph node involvement detection of 90% and 94%. Combining visual ADC analysis with size measurement increased DWI specificity to 100% with 81% sensitivity. For organ involvement, the two techniques agreed in all 20 recorded organs (100%). All involved organ lesions showed restricted diffusion. Ann Arbor stages agreed in 14 (93%) of the 15 patients.Conclusion: Whole-body DWI with ADC analysis can potentially be used for lesion detection and staging in patients with DLBCL. [ABSTRACT FROM AUTHOR]

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials. [ABSTRACT FROM AUTHOR]

In the presentp aper, we study the existence and non-existence results of a positive solution for the Steklov eigenvalue problem driven by nonhomogeneous operator $(p,q)$-Laplacian with indefinite weights. We also prove that in the case where $\mu>0$ and with $10$ there exists an interval of principal eigenvalues for our Steklov eigenvalue problem.

We use the Hardy-Sobolev inequality to study existence and non-existence results for a positive solution of the quasilinear elliptic problem -\Delta{p}u − \mu \Delta{q}u = \limda[mp(x)|u|p−2u + \mu mq(x)|u|q−2u] in \Omega driven by nonhomogeneous operator (p, q)-Laplacian with singular weights under the Dirichlet boundary condition. We also prove that in the case where μ > 0 and with 1 < q < p < \infinity the results are completely different from those for the usual eigenvalue for the problem p-Laplacian with singular weight under the Dirichlet boundary condition, which is retrieved when μ = 0. Precisely, we show that when μ > 0 there exists an interval of eigenvalues for our eigenvalue problem.

Using variational methods, we prove in a different cases the existence and multiplicity of $a$-harmonic solutions for the following elleptic problem:\begin{equation*}\begin{gathered}div(a(x, \nabla u))=0, \quad \text{in }\Omega, \\a(x, \nabla u).\nu=f(x,u), \quad \text{on } \partial\Omega,\end{gathered}\end{equation*} where $\Omega\subset\mathbb{R}^N(N \geq 2)$ is a bounded domain ofsmooth boundary $\partial\Omega$ and $\nu$ is the outward normalvector on $\partial\Omega$. $f: \partial\Omega\times \mathbb{R} \rightarrow \mathbb{R},$ $a: \overline{\Omega}\times \mathbb{R}^{N} \rightarrow\mathbb{R}^{N},$ are fulfilling appropriate conditions.

By applaying the Ricceri's three critical points theorem, we show the existence of at least three solutions to the following elleptic problem: \begin{equation*} \begin{gathered} -div[a(x, \nabla u)]+|u|^{p(x)-2}u=\lambda f(x,u), \quad \text{in }\Omega, \\ a(x, \nabla u).\nu=\mu g(x,u), \quad \text{on } \partial\Omega, \end{gathered} \end{equation*} where $\lambda$, $\mu \in \mathbb{R}^{+},$ $\Omega\subset\mathbb{R}^N(N \geq 2)$ is a bounded domain of smooth boundary $\partial\Omega$ and $\nu$ is the outward normal vector on $\partial\Omega$. $p: \overline{\Omega} \mapsto \mathbb{R}$, $a: \overline{\Omega}\times \mathbb{R}^{N} \mapsto \mathbb{R}^{N},$ $f: \Omega\times\mathbb{R} \mapsto \mathbb{R}$ and $g:\partial\Omega\times\mathbb{R} \mapsto \mathbb{R}$ are fulfilling appropriate conditions.

By applying two versions of Mountain Pass Theorem, we prove two different situations of the existence of solutions for the following Steklov problem $\Delta_{p(x)}u =|u|^{p(x)-2}u$ in $\Omega$, $|\nabla u|^{p(x)-2}\frac{\partial u}{\partial \nu}= \lambda |u|^{q(x)-2}u$ on $\partial\Omega$, where $\Omega$ is a bounded domain in $\mathbb{R}^{N}(N\geq 2)$ with smooth boundary $\partial\Omega$ and $p(.), q(.):\bar{\Omega}\rightarrow (1, +\infty)$ are continuous functions.

In this paper we prove the existence of a weak solution to the following system△_p u = △_q v = 0 in Ω,|∇u|^{p−2} ∂_ν u = f(x,u) − (α + 1)K(x)|u|^{α−1}u|v|^{β+1} + f1 on ∂Ω,|∇v|^{q−2} ∂_ν v = g(x,v) − (β + 1)K(x)|v|^{β−1}v|u|^{α+1} + g1 on ∂Ω,where Ω is a bounded domain in RN (N ≥ 2), f1, g1, f, g and K are functions that satisfy some conditions.

In this paper, we show the existence of a sequences of eigenvalues for an operator homogenous at the infinity, we give his variational formulation and we establish the simplicity of all eigenvalues in the case N = 1. Finally we study thesolvability of the problemA(u) := −div(A(x,∇u)) = f(x, u) + h in Ω,u = 0 on ∂Ω,as well as the spectrum ofG_0'(u) = λm|u|^{p−2}u in Ω,u = 0 on ∂Ω.

In this paper, we prove the existence of weak solutions to the problem △_p u = 0 in Ω, |∇u|^{p−2} ∂_ν u = λ_1 m(x)|u|^{p−2}u + f(x, u) − h on ∂Ω, where Ω is a bounded domain in RN (N ≥ 2), m ∈ L^q(∂Ω) is a weight, λ_1 is the first positive eigenvalue for the eigenvalue Steklov problem △pu = 0 in Ω and |∇u|^{p−2} ∂_ν u=λ m(x)|u|^{p−2}u on ∂Ω. f and h are functions that satisfy some conditions.

abstract: In this paper, we give some properties of the first nonprincipal eigenvalue for an asymmetric Steklov problem with weights, and we study the Fucik spectrum.

In this article, we study the existence of the eigencurves for a Steklov problem and we obtain their variational formulation. Also we prove the simplicity and the isolation results of each point of the principal eigencurve. Also we obtain the continuity and the differentiability of the principal eigencurve.

In this paper we prove existence and uniqueness of classical solutions for the non-autonomous inhomogeneous Cauchy problem $$displaylines{ frac{d}{dt}u(t)=A(t)u(t)+f(t), quad 0 leq sleq tleq T, cr L(t)u(t)=Phi(t)u(t)+g(t) , quad 0leq sleq tleq T, cr u(s)=x. }$$ The solution to this problem is obtained by a variation of constants formula.

Not available.

Background: IMAGE is a retrospective cohort study of patients enrolled in early access programs (EAPs) in France with relapsed/refractory multiple myeloma (RRMM) receiving isatuximab with pomalidomide and dexamethasone (Isa-Pd)., Methods: Patients aged ≥18 years with RRMM who received ≥1 dose of Isa under the EAPs between July 29, 2019 and August 30, 2020 were included. Effectiveness endpoints included progression-free survival (PFS) and response rates. Verbatim terms for adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities and not graded for severity., Results: A total of 294 and 299 patients were included in the effectiveness and safety populations, respectively. IMAGE included patients who received one prior line of treatment (10.2%) and were daratumumab-refractory (19.1%). At median follow-up of 14.2 months, median PFS in the effectiveness population was 12.4 months (95% CI 9.0-15.0). Overall response and very good partial response rates were 46.3% and 27.9%, respectively. Subgroup analyses reflected similar results. In the safety population, 26.4% of patients reported at least one AE; the most common any-grade AE was neutropenia (9.4%)., Conclusion: IMAGE demonstrated Isa-Pd had meaningful effectiveness in median PFS and depth of response and no new safety signals in a real-world context, consistent with clinical trial results., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: Daratumumab-treated myeloma patients may face increased seasonal influenza risk due to weakened postvaccination immune responses, especially with daratumumab treatment. We aimed to assess humoral responses to boosted influenza vaccination in daratumumab-treated or -untreated patients., Methods: In a single-center study, we evaluated humoral responses (hemagglutination-inhibition assay) one month following a two-injection (4-weeks apart) influenza vaccination (standard dose) in 84 patients with multiple myeloma (40 with daratumumab in the past year)., Results: Seroprotection rates (titer ≥1/40) after the second vaccine injection were low across vaccinal subtypes (except for A-H3N2): 71.3% (A-H3N2), 19.7% (A-H1N1pdm09), 9.9% (B-Victoria), 11.3% (B-Yamagata). Only A-H3N2 seroprotection rates significantly increased with the booster in daratumumab-treated patients (30% (12/40) after one injection vs 55% (22/40) after the boost; P = 0.01).After propensity score weighting, daratumumab was not significantly associated with a reduced likelihood of seroprotection against at least one vaccine strain (OR 0.65 [95% CI: 0.22-1.88])., Conclusion: While daratumumab treatment did not lead to a significant reduction in seroprotection rates following influenza vaccination, a booster vaccine injection demonstrated potential benefit for specific strains (A-H3N2) in patients undergoing daratumumab treatment. Nevertheless, the overall low response rates in patients with multiple myeloma necessitates the development of alternative vaccination and prophylaxis strategies., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F. Lemonnier received research funding from Institut Roche and travel grant from Gilead, G. Melica received honoraria from lectures from Astellas, Pfizer, Gilead, MSD, Janssen. S. Fourati received research grants from Moderna, and consulting fees from Moderna, Astrazeneca, Pfizer, GSK and Cepheid, as well as support for traval from Astellas, Gilead and Pfizer. C. Haioun received research funding and consulting honoraria for lectures from Amgen, Celgen, Gilead, Janssen, Novartis, F.Hoffmann-La Roche, Servier, Takeda, Miltenyi. F. Lemonnier received research funding from La Roche Institute and support for attending meetings from Gilead. F. Le Bras received research funding from Takeda and Celgene BMS, and honoraria from Takeda, Kite Gilead and Novartis. K. Belhadj received nonfinancial research support from AbbVie., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA., Methods: CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383., Findings: Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001)., Interpretation: The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma., Funding: Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development., Competing Interests: Declaration of interests PM served on advisory boards for and received honoraria from Janssen, Bristol Myers Squibb, Amgen, Takeda, AbbVie, Sanofi, and Pfizer. CH received honoraria from Janssen, Bristol Myers Squibb, Amgen, AbbVie, and Pfizer. AP served in a consulting or advisory role for Bristol Myers Squibb, Janssen, and Pfizer; and received research funding from Bristol Myers Squibb, Sanofi, and Takeda. BA received research funding (paid to institution) from Bristol Myers Squibb; received honoraria from Janssen, Bristol Myers Squibb, Sanofi, and GSK; received travel funding from Janssen, Bristol Myers Squibb, and Sanofi; and served on an advisory board for Janssen, Bristol Myers Squibb, and Takeda. KB has a direct financial relationship with Janssen, Bristol Myers Squibb, Amgen, Sanofi, and Pfizer. SZ received research support from Janssen and Takeda; and served on advisory boards for Janssen, Bristol Myers Squibb, Sanofi, Oncopeptides, Amgen, and Takeda. MD received honoraria from and served in a consulting or advisory role for Amgen, Bristol Myers Squibb, Janssen, Sanofi, and Stemline; and received research funding from Janssen. CS received consulting fees or honoraria from Takeda, Bristol Myers Squibb, Janssen, Amgen, Sanofi, and Pfizer. MMo received honoraria from Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Celgene, Janssen, Takeda, Novartis, and Sanofi; and received research funding from Celgene, Janssen, and Sanofi. LK received honoraria from, served on advisory boards for, or received travel funding from AbbVie, Amgen, Janssen, Celgene/Bristol Myers Squibb, Pfizer, Sanofi, and Takeda. MMa received honoraria from and served in a consulting or advisory role for Janssen, Bristol Myers Squibb/Celgene, Sanofi, and Takeda; received research funding from Janssen and Takeda; and received travel, accommodations, or expenses from Janssen and Sanofi. FO-P served on boards for Janssen, Sanofi, and Pfizer. MR served on an advisory board for Janssen and Pfizer; received research funding from Bristol Myers Squibb, Janssen, and Sanofi; gave lectures for Amgen, Bristol Myers Squibb, Janssen, and Takeda; and had travel, accommodations, or other expenses paid or reimbursed by Amgen, Bristol Myers Squibb, GSK, Janssen, Pfizer, Sanofi, and Takeda. JMSdC served on an advisory board and received honoraria from Janssen, Sanofi, GSK, and AbbVie; and received accommodations from Pfizer and Amgen. NWCJvdD received research support from Janssen, Amgen, Celgene, Novartis, Cellectis, and Bristol Myers Squibb; and serves on advisory boards for Janssen, Amgen, Celgene, Bristol Myers Squibb, Sanofi, Takeda, Roche, Novartis, Bayer, Adaptive, Merck, Pfizer, AbbVie, and Servier (all paid to institution). AB served on advisory boards for Janssen, Sanofi, Amgen, and Bristol Myers Squibb. CT served on an advisory board for and received honoraria from Janssen. NM served on an advisory board for Janssen. M-CV received travel support from Janssen and Sanofi. M-DL received travel expenses from Janssen. WH is an employee of Cytel and is a contractor for Johnson & Johnson. JW, CdB, MR, VV, RC, and JV are employees of Janssen and hold stock in Johnson & Johnson. AT is an employee of Janssen. JC served on advisory boards for Sanofi and Bristol Myers Squibb; served as a consultant for Janssen, Sanofi, Bristol Myers Squibb, Pfizer, and Adaptive; received research support from Sanofi and Bristol Myers Squibb; and received travel support from Janssen, Sanofi, Bristol Myers Squibb, and Pfizer. PS served on an advisory board for Amgen, Bristol Myers Squibb, Celgene, Janssen, Karyopharm, and Pfizer; and received research funding from Amgen, Bristol Myers Squibb, Celgene, Janssen, and Karyopharm. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 -5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 -5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10 -5 and 10 -6 , and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 -5 , the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 ., (© 2024. The Author(s).)

A second autologous stem-cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti-CD38 and immunotherapy, its role remains debated. We conducted a real-life study in 10 French centers (1996-2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event-free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3-2.8), and 2-year EFS estimate was 63% (95% CI: 57-70). Median overall survival (OS) was 8.1 years (95% CI: 5.9-NA), and 2-year OS estimate was 92% (95% CI: 88-95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3-0.9, p  = 0.012 and HR: 0.4; 95% CI: 0.3-0.6, p  < 0.001, respectively) and OS (HR: 0.4; 95% CI: 0.2-0.9, p  = 0.017 and HR: 0.2; 95% CI: 0.1-0.4, p  < 0.001, respectively), while male sex correlated with poorer outcomes for EFS (HR: 2.5; 95% CI: 1.7-3.7, p  < 0.001) and OS (HR: 2.7; 95% CI: 1.4-4.9, p  = 0.002). Overall, ASCT2 appeared efficient with low toxicity in RMM. Maintenance therapy was associated with extended EFS and OS, particularly in patients with VGPR+ status post ASCT2. These findings underscore ASCT2's potential in RMM when coupled with maintenance therapy in selected patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Competing Interests: Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abstract: Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The RAS/RAF pathway is the most frequently mutated, in ∼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event. Because these genes are part of our routine next-generation sequencing panel, we analyzed >10 000 patients with different plasma cell disorders to describe the RAS/RAF landscape. In this large cohort of patients, almost 61% of the patients presented a RAS/RAF mutation at diagnosis or relapse, but much lower frequencies occurred in presymptomatic cases. Of note, the mutations were different from that observed in solid tumors (higher proportions of Q61 mutations). In 29 patients with 2 different mutations, we were able to perform single-cell sequencing, showing that in most cases, mutations occurred in different subclones, suggesting an ongoing mutational process. These findings suggest that the RAS/RAF pathway is not an attractive target, both on therapeutic and residual disease assessment points of view., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Aims: Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage., Methods and Results: This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision-making regarding therapy. Over the 12-year study period, among the 233 patients included, 133 were NYHA III-IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT-proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut-off values for Stage 1: hsTnT ≤ 107 ng/L and NT-proBNP ≤ 3867 ng/L (n = 77; 33%); for stage 2 NT-proBNP > 3867 ng/L (n = 72; 30%). For stage 3, if troponin >107 ng/L, regardless of NT-proBNP then CB 4 μmol/L, was added (n = 41; 17.5%) and stage 4: CB > 4 μmol/L (n = 43; 18.5%). The median overall survival was 8 months 95% CI [2-24]. At 1 year, 102 (44%) patients died and the Kaplan-Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2 months (95% CI [11-18]) and stage 3, 6.6 months (95% CI [1-13]). Notably, among European stage II patients, 17.1%, n = 8 were MACS stage 3 and European stage IIIb 21.4% (n = 23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n = 29) were classified MACS stage 4 and 12.5% n = 9 were only MACS stage 2., Conclusions: The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Providing the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM., Methods: An integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04)., Results: The primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (≥ VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the ≥ VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04)., Conclusion: These results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658)., Competing Interests: LR and JL report honoraria from Janssen; Celgene, a Bristol-Myers Squibb Company; Takeda; and Amgen. AO reports consultancy and speakers bureau with Amgen; Janssen; Takeda; and Celgene, a Bristol-Myers Squibb Company. RR reports consultancy with Amgen; Celgene, a Bristol-Myers Squibb Company; Janssen; and Takeda. CH reports honoraria from Celgene, a Bristol-Myers Squibb Company; Janssen; Takeda; and Amgen. AS reports honoraria from Bristol Myers Squibb, Takeda, Sanofi, Merck, and Roche; consultancy with Bristol Myers Squibb, Takeda, and Merck; and speakers bureau with Takeda. M-VM reports honoraria and membership on advisory boards with Janssen; Celgene, a Bristol-Myers Squibb Company; Amgen; Takeda; AbbVie; GlaxoSmithKline; EDO; PharmaMar; and Adaptive. MM reports honoraria, membership on advisory boards, and financial support with Celgene, a Bristol-Myers Squibb Company; Janssen; and Takeda and honoraria and membership on advisory boards with Amgen. JS-M reports consultancy with Bristol Myers Squibb; Celgene, a Bristol-Myers Squibb Company; Novartis; Takeda; Amgen; MSD; Janssen; and Sanofi and membership on board of directors or advisory committees with Takeda. KB reports honoraria and consultancy with Celgene, a Bristol-Myers Squibb Company; Amgen; Janssen; and Takeda. MG reports employment with Celgene, a Bristol-Myers Squibb Company. JB reports honoraria from Janssen; Celgene, a Bristol-Myers Squibb Company; and Amgen. PM reports honoraria from Celgene, a Bristol-Myers Squibb Company; Janssen; Takeda; AbbVie; and Amgen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Celgene, a Bristol-Myers Squibb Company. Author MG was employed by the funder and involved in study design, collection, analysis, or interpretation of data and writing the article and deciding to submit the article for publication., (Copyright © 2023 Rosiñol, Hebraud, Oriol, Colin, Ríos Tamayo, Hulin, Blanchard, Caillot, Sureda, Hernández, Arnulf, Mateos, Macro, San-Miguel, Belhadj, Lahuerta, Garelik, Bladé and Moreau.)

Background: Early cardiac amyloidosis (CA) diagnosis enables patients to access effective treatments for better long-term outcomes, yet it remains under-recognised, misdiagnosed and inadequately managed., Aim: To reduce diagnostic delays, we aimed to describe the epidemiological and clinical characteristics and changes over an 11-year period., Methods: This was a retrospective, observational cohort study of all patients referred to the Henri-Mondor Hospital for suspected CA., Results: Overall, 3194 patients were identified and 3022 were included and analysed. Our patients came from varied ethnic backgrounds, and more than half (55.2%) had confirmed CA. Over 11 years, referrals increased 4.4-fold, mostly from cardiologists. Notably, wild-type transthyretin amyloidosis (ATTRwt) became the predominant diagnosis, with referrals increasing 15-fold from 20 in 2010-2012 to 308 in 2019-2020. The number of amyloid light chain (AL) diagnoses increased, whilst variant transthyretin amyloidosis (ATTRv) numbers remained relatively stable. Concerning disease severity, AL patients presented more frequently with severe cardiac involvement whereas an increasing number of ATTRwt patients presented with National Amyloid Centre stage I (22.0% in 2013-2014 to 45.9% in 2019-2020). Lastly, among patients diagnosed with ATTRv in 2019-2020, 83.9% had ATTR Val122Ile cardiac phenotype., Conclusions: This study shows that increasing cardiologist awareness and referrals have increased CA diagnoses. With improved awareness and non-invasive diagnostic techniques, more patients with ATTRwt with milder disease and more ATTRv Val122Ile mutations are being referred and diagnosed. Although more AL cases are being recognised, patients are diagnosed with severe cardiac involvement., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28-day cycles of pomalidomide 4 mg daily on days 1-21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow-up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression-free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug-related non-haematological AEs (>5%) comprised 13% infections. Long-term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)