Safety and feasibility of stem cell boost as a salvage therapy for severe hematotoxicity after CD19 CAR T-cell therapy

Stem cell; Hematotoxicity; T-cellCélulas madre; Hematotoxicidad; Células TCèl·lules mare; Hematotoxicitat; Cèl·lules TThis work was supported by a fellowship from School of Oncology of German Cancer Consortium (DKTK) (K.R.) and was funded by the Else Kröner Forschungskolleg; a Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) research grant provided within the Sonderforschungbereich (SFB-TRR 388/1 2021–452881907) and DFG research grant (451580403) (M.S.); the Bavarian Elite Graduate Training Network (M.S.), the Wilhelm-Sander Stiftung (project no. 2018.087.1) (M.S.), the Else-Kröner-Fresenius Stiftung (M.S., K.R., V. Bücklein, V. Blumenberg), and the Bavarian Center for Cancer Research (BZKF)

The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL

Hematological toxicity; Infectious complicationsToxicidad hematológica; Complicaciones infecciosasToxicitat hematològica; Complicacions infecciosesCD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0–1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not-reached, p < .0001), and OS (median 26 months vs. not-reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes.KR received a fellowship from the School of Oncology of the German Cancer Consortium (DKTK) and was funded by the Else Kröner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP). This work was supported by a grant within the Gilead Research Scholar Program (to KR, MS), the Bruno & Helene Jöster foundation (to KR, MS), and by a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 388/12021–452881907 and DFG research grant 451580403 (to MS). This work was in part supported by NCI/NIH P30CA076292. FLL is in part supported as a Clinical Scholar by the Leukemia and Lymphoma Society. The work was further supported by the Bavarian Elite Graduate Training Network (to MS), the Wilhelm-Sander Stiftung (to MS, project no. 2018.087.1), the Else-Kröner-Fresenius Stiftung (to MS), and the Bavarian Center for Cancer Research (BZKF)

The CAR‐HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL

CD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0–1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not-reached, p < .0001), and OS (median 26 months vs. not-reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes

Cartographie d'impédance par inversion d'un code d'électromagnétisme 3D surfacique

International audienceThis article is dedicated to the problem of reconstructing the surface impedance of a three-dimensional object. It is based on the measurement of backscattering coefficients by a monostatic radar. This problem requires the costly resolution of Maxwell's equations. First we present how it is possible to reduce it to a direct model, based on the linearization of Maxwell's equations in integral form within a 3D electromagnetism numerical code. Then, two reconstruction methods are proposed based on the minimization of convex penalized criteria ; they are validated on simulated data.Cet article est dédié au problème de la reconstruction d'impédance surfacique d'un objet tridimensionnel. Il se base sur la mesure de coefficients de rétrodiffusion par un radar monostatique. Il s'agit d'un problème qui nécessite la résolution coûteuse des équations de Maxwell. Dans un premier temps on présente comment, en s'appuyant sur la linéarisation des équations de Maxwell sous forme intégrale au sein d'un code de calcul d'électromagnétisme 3D, il est possible de se ramener à un modèle direct. Puis, on propose deux méthodes de reconstruction fondées sur la minimisation de critères pénalisés convexes ; elles sont validées sur des données simulées

B-cell malignancies and COVID-19: a narrative review

International audienceBackground. COVID-19 has been extensively characterized in immunocompetent hosts and to a lesser extent in immunocompromised populations. Among the latter, patients treated for Bcell malignancies have immunosuppression generated by B-cell lymphodepletion/aplasia resulting in a higher susceptibility to respiratory virus infections and poor response to vaccination. The consequence is that these patients are likely to develop severe or critical COVID-19. Objectives. To examine the overall impact of COVID-19 in patients treated for a B-cell malignancy or receiving chimeric antigen receptor T (CAR-T) immunotherapy administered in case of relapsed or refractory disease. Sources. We searched in the Medline database to identify relevant studies, trials, reviews, or meta-analyses focusing on SARS-CoV-2 vaccination or COVID-19 management in patients treated for a B-cell malignancy or recipients of CART cell therapy up to July 8 th , 2022. Content. The epidemiology and the outcomes of COVID-19 in B-cell malignancy patients and CART cell recipients are summarized. Vaccine efficacy in these subgroups is compiled. Considering the successive surges of variants of concern, we propose a critical appraisal of treatment strategies by discussing the use of neutralizing monoclonal antibodies, convalescent plasma therapy, direct-acting antiviral drugs, corticosteroids and immunomodulators. Implications. For B-cell malignancy patients, preventive vaccination against SARS-CoV-2 remain essential and management of COVID-19 includes the control of viral replication due to protracted SARS-CoV-2 shedding. Passive immunotherapy (monoclonal neutralizing antibody therapy, convalescent plasma therapy) and direct-active antivirals such as remdesivir and nirmatrelvir/ritonavir are the best currently available treatments. Real-world data and subgroup analyses in larger trials are warranted to assess COVID-19 therapeutics in B-cell depleted populations

Management of choroidal metastasis using external beam radiotherapy: a retrospective study and review of the literature

Aim: Choroidal metastases are rare in the evolution of solid cancers and constitute exceptional metastatic sites involving functional visual prognosis. The authors conducted a retrospective study to determine the interest of external radiotherapy for the treatment of choroidal metastases.Methods: The authors reviewed the records of 28 patients with choroidal metastases who had breast (n = 15), lung (n = 9), ovarian (n = 1), kidney (n = 1), prostate (n = 1) cancer or carcinoma with unknown primitive at the moment of the diagnosis (n = 1). The median age was 58 years (extremes: 34-71 years). Tumor stage before the discovery of metastatic choroidal metastasis was 50% of patients. Ocular involvement was unilateral (n = 22) or bilateral (n = 6). The delivered doses ranged from 20 to 50 Gy fractionated with 3-5 Gy in 2D technique (n = 5), conformational (n = 21), intensity modulation (n = 2). The most widely used prescription scheme delivered 30 Gy in 10 fractions (64%) using two 6 MV photons beams. Results: At the end of irradiation, 13 patients (46%) showed an improvement of eye symptoms. For the others, a stabilization in symptoms was noted (n = 15). No patient had visual degradation. No acute or late grade 2-3 toxicities were objectified. The histological type did not influence the response (P = 0.5). There was no dose relationship-response in our series.Conclusion: External radiation therapy is a useful technique in the palliative treatment of choroidal metastases. Acute and late toxicities are acceptable

An 18F-FDG-PET maximum standardized uptake value > 10 represents a novel valid marker for discerning Richter’s Syndrome

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Metagenomic Next-Generation Sequencing Reveals Individual Composition and Dynamics of Anelloviruses during Autologous Stem Cell Transplant Recipient Management

Over recent years, there has been increasing interest in the use of the anelloviruses, the major component of the human virome, for the prediction of post-transplant complications such as severe infections. Due to an important diversity, the comprehensive characterization of this viral family over time has been poorly studied. To overcome this challenge, we used a metagenomic next-generation sequencing (mNGS) approach with the aim of determining the individual anellovirus profile of autologous stem cell transplant (ASCT) patients. We conducted a prospective pilot study on a homogeneous patient cohort regarding the chemotherapy regimens that included 10 ASCT recipients. A validated viral mNGS workflow was used on 108 plasma samples collected at 11 time points from diagnosis to 90 days post-transplantation. A complex interindividual variability in terms of abundance and composition was noticed. In particular, a strong sex effect was found and confirmed using quantitative PCR targeting torque teno virus, the most abundant anellovirus. Interestingly, an important turnover in the anellovirus composition was observed during the course of the disease revealing a strong intra-individual variability. Although more studies are needed to better understand anellovirus dynamics, these findings are of prime importance for their future use as biomarkers of immune competence

Refractory diffuse large B-cell lymphoma after first-line immuno-CT: Treatment options and outcomes

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