Publications by authors named "Catherine Thieblemont"

208 Publications

A guide to ComBat harmonization of imaging biomarkers in multicenter studies.

J Nucl Med 2021 Sep 16. Epub 2021 Sep 16.

Institut Curie, Universite PSL, Inserm, U1288 LITO, Universite Paris Saclay, France.

The impact of PET image acquisition and reconstruction parameters on SUV measurements or radiomic feature values is widely documented. This "scanner" effect is detrimental to the design and validation of predictive or prognostic models and limits the use of large multicenter cohorts. To reduce the impact of this scanner effect, the ComBat method has been proposed and is now used in various contexts. The purpose of this article is to explain and illustrate the use of ComBat based on practical examples. We also give examples in which the ComBat assumptions are not met; thus, ComBat should not be used.
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http://dx.doi.org/10.2967/jnumed.121.262464DOI Listing
September 2021

The Magnolia Trial: Zanubrutinib, A Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma.

Clin Cancer Res 2021 Sep 15. Epub 2021 Sep 15.

BeiGene USA, Inc.

Purpose: Marginal zone lymphoma (MZL) is an uncommon non-Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL.

Experimental Design: Patients with R/R MZL were enrolled in the phase 2 MAGNOLIA (BGB-3111-214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification.

Results: Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months.with the majority of adverse events (AEs) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in two patients; one patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, four patients discontinued treatment due to AEs, none of which was considered treatment-related by the investigators.

Conclusions: Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1704DOI Listing
September 2021

Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes.

Clin Lymphoma Myeloma Leuk 2021 Jul 22. Epub 2021 Jul 22.

Institute Jules Bordet, Brussels, Belgium.

Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor.

Patients And Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate.

Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels ≥ 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups.

Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin.
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http://dx.doi.org/10.1016/j.clml.2021.07.017DOI Listing
July 2021

Oncogenic HSP90 facilitates metabolic alterations in aggressive B-cell lymphomas.

Cancer Res 2021 Sep 3. Epub 2021 Sep 3.

Division of Hematology and Medical Oncology, Weill Cornell Medical College and New York Presbyterian Hospital

HSP90 is critical for the maintenance of cellular proteostasis. In cancer cells, HSP90 also becomes a nucleating site for the stabilization of multiprotein complexes including signaling pathways and transcription complexes. Here we describe the role of this HSP90 form, referred to as oncogenic HSP90, in the regulation of cytosolic metabolic pathways in proliferating B-cell lymphoma cells. Oncogenic HSP90 assisted in the organization of metabolic enzymes into non-membrane-bound functional compartments. Under experimental conditions that conserved cellular proteostasis, oncogenic HSP90 coordinated and sustained multiple metabolic pathways required for energy production and maintenance of cellular biomass as well as for secretion of extracellular metabolites. Conversely, inhibition of oncogenic HSP90, in the absence of apparent client protein degradation, decreased the efficiency of MYC-driven metabolic reprogramming. This study reveals that oncogenic HSP90 supports metabolism in B-cell lymphoma cells and patients with diffuse large B-cell lymphoma, providing a novel mechanism of activity for HSP90 inhibitors.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-2734DOI Listing
September 2021

Kidney Transplant T-Cell-Mediated Rejection Occurring After Anti-CD19 CAR T-Cell Therapy for Refractory Aggressive Burkitt-like Lymphoma With 11q Aberration: A Case Report.

Am J Kidney Dis 2021 Aug 27. Epub 2021 Aug 27.

Nephrology - Kidney Transplant Unit, Rouen University Hospital, 76031, Rouen, France.

Post-transplant lymphoproliferative disorder is a growing complication of kidney transplantation (KT) associated with a dismal prognosis. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a game-changing treatment option modifying the outcome of refractory hematological cancers. Here, we report the case of a 40-year-old KT patient who developed a Burkitt-like Lymphoma with 11q aberration five years after KT. After three unsuccessful lines of chemotherapy, it was decided to treat the patient with anti-CD19 CAR-T cells as a salvage therapy. Three months after CAR-T cell infusion, she experienced a grade II-B T-Cell-mediated rejection with severe tubulitis (T3), slight interstitial inflammation (I1) and severe intimal arteritis (V2) with blood suffusion. Among T-cells infiltrating the graft, some of them expressed the anti-CD19 CAR. CAR-T cells within the graft and in blood samples were also evidenced by droplet digital PCR. KT function improved after corticosteroids treatment and remained stable. However, lymphoma progressed with a massive pulmonary mass leading to the patient's death 10 months after CAR-T cell infusion.
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http://dx.doi.org/10.1053/j.ajkd.2021.07.012DOI Listing
August 2021

Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial.

Lancet Haematol 2021 Sep;8(9):e648-e657

Department of Medicine III, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Institute of Medical Information Processing, Biometry and Epidemiology, Ludwig Maximilian University of Munich, Munich, Germany.

Background: Autologous haematopoietic stem-cell transplantation (HSCT) in first remission is the current standard treatment in fit patients with mantle cell lymphoma. In this long-term follow-up study, we aimed to evaluate the efficacy of autologous HSCT versus interferon alfa maintenance after chemotherapy without or with rituximab in patients with primary advanced-stage mantle cell lymphoma.

Methods: We did a post-hoc, long-term analysis of an open-label, multicentre, randomised, phase 3 trial done in 121 participating hospitals or practices across six European countries. Patients who were aged 18-65 years with previously untreated stage III-IV mantle cell lymphoma and an ECOG performance score of 0-2 were eligible for participation. Patients were randomly assigned (1:1) to receive either myeloablative radiochemotherapy (fractionated total body irradiation with 12 Gy/day 6-4 days before autologous HSCT and cyclophosphamide 60 mg/kg per day intravenously 3-2 days before autologous HSCT) followed by autologous HSCT (the autologous HSCT group) or interferon alfa maintenance (the interferon alfa maintenance group; 6 × 10 IU three times a week subcutaneously until progression) after completion of CHOP-like induction therapy (cyclophosphamide 750 mg/m intravenously on day 1, doxorubicin 50 mg/m intravenously on day 1, vincristine 1·4 mg/m [maximum 2 mg] intravenously on day 1, and prednisone 100 mg/m orally on days 1-5; repeated every 21 days for up to 6 cycles) without or with rituximab (375 mg/m intravenously on day 0 or 1 of each cycle; R-CHOP). The primary outcome was progression-free survival from end of induction until progression or death among patients who had a remission and the secondary outcome was overall survival from the end of induction until death from any cause. We did comparisons of progression-free survival and overall survival according to the intention-to-treat principle between both groups among responding patients and explored efficacy in subgroups according to induction treatment without or with rituximab. Hazard ratios (HRs) were adjusted for the mantle cell lymphoma international prognostic index (MIPI) numerical score, and in the total group also for rituximab use (adjusted HR [aHR]). This trial was started before preregistration was implemented and is therefore not registered, recruitment is closed, and this is the final evaluation.

Findings: Between Sept 30, 1996, and July 1, 2004, 269 patients were randomly assigned to receive either autologous HSCT or interferon alfa maintenance therapy. The median follow-up was 14 years (IQR 10-16), with the intention-to-treat population consisting of 174 patients (93 [53%] in the autologous HSCT group and 81 [47%] in the interferon alfa maintenance group) who responded to induction therapy. The median age was 55 years (IQR 47-60), and R-CHOP was used in 68 (39%) of 174 patients. The median progression-free survival was 3·3 years (95% CI 2·5-4·3) in the autologous HSCT group versus 1·5 years (1·2-2·0) in the interferon alfa maintenance group (log-rank p<0·0001; aHR 0·50 [95% CI 0·36-0·69]). The median overall survival was 7·5 years (95% CI 5·7-12·0) in the autologous HSCT group versus 4·8 years (4·0-6·6) in the interferon alfa maintenance group (log-rank p=0·019; aHR 0·66 [95% CI 0·46-0·95]). For patients treated without rituximab, the progression-free survival adjusted HR for autologous HSCT versus interferon alfa was 0·40 (0·26-0·61), in comparison to 0·72 (0·42-1·24) for patients treated with rituximab. For overall survival, the adjusted hazard ratio for HSCT versus interferon alfa was 0·52 (0·33-0·82) without rituximab and 1·05 (0·55-1·99) for patients who received rituximab.

Interpretation: Our results confirm the long-term efficacy of autologous HSCT to treat mantle cell lymphoma established in the pre-rituximab era. The suggested reduced efficacy after immunochemotherapy supports the need for its re-evaluation now that antibody maintenance, high-dose cytarabine, and targeted treatments have changed the standard of care for patients with mantle cell lymphoma.

Funding: Deutsche Krebshilfe, the European Community, and the Bundesministerium für Bildung und Forschung, Kompetenznetz Maligne Lymphome.
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http://dx.doi.org/10.1016/S2352-3026(21)00195-2DOI Listing
September 2021

New Approaches in Characterization of Lesions Dissemination in DLBCL Patients on Baseline PET/CT.

Cancers (Basel) 2021 Aug 8;13(16). Epub 2021 Aug 8.

LITO Laboratory, U1288, Institut Curie, Université PSL, Inserm, Université Paris Saclay, 91400 Orsay, France.

Dissemination, expressed recently by the largest Euclidian distance between lymphoma sites (SDmax), appeared a promising risk factor in DLBCL patients. We investigated alternative distance metrics to characterize the robustness of the dissemination information. In 290 patients from the REMARC trial (NCT01122472), the Euclidean (Euc), Manhattan (Man), and Tchebychev (Tch) distances between the furthest lesions, firstly based on the centroid of each lesion and then directly from the two most distant tumor voxels and the Travelling Salesman Problem distance (TSP) were calculated. For PFS, the areas under the ROC curves were between 0.63 and 0.64, and between 0.62 and 0.65 for OS. Patients with high SDmax whatever the method of calculation or high SD_TSP had a significantly poorer outcome than patients with low SDmax or SD_TSP ( < 0.001 for both PFS and OS), with significance maintained in Ann Arbor advanced-stage patients. In multivariate analysis with total metabolic tumor volume and ECOG, each distance feature had an independent prognostic value for PFS. For OS, only SDmax_Tch, SDmax_Euc _Vox, and SDmax_Man _Vox reached significance. The spread of DLBCL lesions measured by the largest distance between lymphoma sites is a strong independent prognostic factor and could be measured directly from tumor voxels, allowing its development in the area of the deep learning segmentation methods.
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http://dx.doi.org/10.3390/cancers13163998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392801PMC
August 2021

Concomitant occurrence of genetically distinct Hodgkin lymphoma and primary mediastinal lymphoma.

Clin Case Rep 2021 Aug 16;9(8):e04504. Epub 2021 Aug 16.

Department of Clinical Hematology Centre Henri Becquerel, INSERM U1245 Rouen France.

Synchronous Hodgkin Lymphoma and Primary Mediastinal B-cell Lymphoma is possible, with molecular analyses proving the absence of clonal filiation between both entities. This suggests a common etiology but the existence of two divergent clones.
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http://dx.doi.org/10.1002/ccr3.4504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365538PMC
August 2021

Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.

Br J Haematol 2021 Aug 22;194(4):690-700. Epub 2021 Jul 22.

University Medical Center Groningen, Groningen, Netherlands, on behalf of HOVON/PPLC.

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 10  CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.
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http://dx.doi.org/10.1111/bjh.17527DOI Listing
August 2021

Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study.

J Hematol Oncol 2021 07 16;14(1):111. Epub 2021 Jul 16.

Karyopharm Therapeutics, Newton, USA.

Patients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of < 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were ≥ 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months (p < 0.0001). Patients < 70 years had an OS of 11.1 months compared with 7.8 months in patients ≥ 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be < 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned. This trial was registered at ClinicalTrials.gov (NCT02227251) on August 28, 2014. https://clinicaltrials.gov/ct2/show/NCT02227251 .
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http://dx.doi.org/10.1186/s13045-021-01122-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283921PMC
July 2021

Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy.

Am J Hematol 2021 08 12;96(8):934-944. Epub 2021 May 12.

Service d'Hématologie Oncologie, Centre Hospitalier de Versailles, Le Chesnay, France.

Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19-92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1-235). After a median follow-up of 191 days (3-260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42-3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04-4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
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http://dx.doi.org/10.1002/ajh.26209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212109PMC
August 2021

Outcome after hematopoietic stem cell transplantation in patients with extranodal natural killer/T-Cell lymphoma, nasal type: A French study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Am J Hematol 2021 07 3;96(7):834-845. Epub 2021 May 3.

Department of Hematology, Inserm U1163, IMAGINE Institute, Paris University, Necker Hospital, Paris, France.

We evaluated the outcome of 65 French patients with Extranodal NK/T-cell lymphoma, nasal type (ENKTL) undergoing hematopoietic stem cell transplantation (HSCT) (19 allogeneic and 46 autologous). Fifty-four patients (83%), most of which receiving L-asparaginase (L-aspa) containing regimens (81%), achieved complete or partial response at time of HCST. After a median follow-up of 79.9 months, 4-years progression-free survival (PFS) and overall survival (OS) were similar in both autologous and allogeneic groups (PFS: 34% vs. 26%, p = .12 and OS: 52% vs. 53%, p = .74). Response status at HSCT was the major independent prognostic factor on survival (OS: HR: 4.013 [1.137; 14.16], p = .031 and PFS: HR: 5.231 [1.625; 16.838], p = .006). As compared to control patients receiving chemotherapy and/or radiotherapy containing regimens only, upfront HSCT did not improve the outcome of responder patients, including those treated by L-aspa. However, it tends to provide survival benefit for relapsed patients with initial high-risk clinical features who achieved second remission. Whereas the place of HSCT in upfront therapy has still to be clarified, these data confirm that HSCT should be considered for consolidation in selected patients with relapsed ENKTL. Based on a large non Asian ENKTL cohort since the L-aspa era, this study provides some insight into the survival patterns of ENKTL patients with HSCT in the Western hemisphere and may give future direction for the next clinical trial design.
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http://dx.doi.org/10.1002/ajh.26200DOI Listing
July 2021

Evaluation of mid-term (6-12 months) neurotoxicity in B-cell lymphoma patients treated with CAR T cells: a prospective cohort study.

Neuro Oncol 2021 Sep;23(9):1569-1575

Service de Neurologie, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Paris, France.

Background: Chimeric antigen receptor-modified T (CAR T) cells are profoundly changing the standard of care in B-cell malignancies. This new therapeutic class induces a significant number of acute neurotoxicity, but data regarding mid- and long-term neurological safety are scarce. We evaluated mid-term neurological safety, with special emphasis on cognitive functions, in a series of adults treated with CAR T cells.

Methods: Patients treated in a single center with CD19-targeted CAR T cells for a relapsing B-cell lymphoma were prospectively followed up by neurologists. Before CAR T-cell infusion, all patients underwent neurological examinations with neuropsychological testing and filled out questionnaires assessing anxiety, depression, and cognitive complaints. Patients surviving without tumor progression were re-evaluated similarly, 6-12 months later.

Results: In this prospective cohort of 56 consecutive adult patients treated with CAR T cells, 27 were eligible for mid-term evaluation (median time 7.6 months). Twelve patients developed an acute and reversible neurotoxicity with median duration time of 5.5 days. In all patients, neurological examination on mid-term evaluation was similar to baseline. In self-assessment questionnaires, 63% of patients reported clinically meaningful anxiety, depression, or cognitive difficulties at baseline, a number reduced to 44% at the time of mid-term evaluation. On cognitive assessments, no significant deterioration was found when compared to baseline, in any cognitive functions assessed (verbal and visual memory, executive functions, language, and praxis), even in patients who developed acute neurotoxicity.

Conclusion: In this cohort of patients treated with CD19-targeted CAR T cells, we found no evidence for neurological or cognitive toxicity, 6-12 months after treatment.
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http://dx.doi.org/10.1093/neuonc/noab077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408887PMC
September 2021

Real-life targeted next-generation sequencing for lymphoma diagnosis over 1 year from the French Lymphoma Network.

Br J Haematol 2021 06 25;193(6):1110-1122. Epub 2021 Mar 25.

Pathology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.

As the impact of targeted next-generation sequencing (TNGS) on daily diagnosis has not been evaluated, we performed TNGS (46 genes) on lymphomas of unclear subtype following expert haematopathological review. The potential impact on patient care and modifications of final diagnosis were divided into major and minor changes according to the European Society of Medical Oncology (ESMO) guidelines. Among 229 patients [19 primary central nervous system lymphomas (PCNSL), 48 large B-cell lymphomas (LBCLs), 89 small BCLs (SBCLs), seven Hodgkin lymphomas (HL), 66 T-cell lymphomas], the overall concordance rate of histological and TNGS diagnosis was 89·5%. TNGS confirmed the histological diagnosis in 144 cases (62·9%), changed the diagnosis in 24 cases (10·5%) and did not help to clarify diagnosis in 61 cases (26·7%). Modifications to the final diagnosis had a clinical impact on patient care in 8·3% of cases. Diagnostic modifications occurred in all types of lymphoma except in PCNSL and HL; the modification rate was 14·6% in SBCL and 12·5% in LBCL. While comparing informative and uninformative cases, no differences were found in terms of DNA amplification, quality or depth of sequencing and biopsy type. The present study highlights that TNGS may directly contribute to a more accurate diagnosis in difficult-to-diagnose lymphomas, thus improving the clinical management in routine practice.
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http://dx.doi.org/10.1111/bjh.17395DOI Listing
June 2021

Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial.

Bone Marrow Transplant 2021 07 3;56(7):1700-1709. Epub 2021 Mar 3.

Department of Clinical Hematology, Nantes University Hospital, Nantes, France.

LyMA trial has demonstrated the benefit of rituximab maintenance after autologous stem cell transplantation (ASCT) in previously untreated mantle-cell lymphoma patients (MCL). Induction consisted of four courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and platinum derivative). The platinum derivative (PD) choice was free: R-DHA-cisplatin, R-DHA-carboplatin, or R-DHA-oxaliplatin. We investigated the prognostic impact of each PD. PFS and OS calculated from inclusion and investigated in an intention-to-treat (ITT) (= 298) and per-protocol analyses (PP) (n = 227). R-DHACis, R-DHACa, or R-DHAOx were used at first cycle in 184, 76, and 38 patients, respectively. Overall, 71 patients (59 in the R-DHACis) required a change in PD, mainly because of PD toxicity. In ITT-analysis, PFS in the R-DHACis and R-DHACa groups were similar (4-year PFS of 65%), while R-DHAOx had a better PFS (4-year PFS of 65% versus 86.5%, respectively, HR = 0.44, p = 0.02). The 4-year OS was 92% for R-DHAOx versus 75.9% for R-DHACis/DHACa (HR = 0.37, p = 0.03). Similar results were yielded in the PP analysis. Low MIPI and R-DHAOx were independent favorable prognostic markers for both PFS (HR = 0.44, p = 0.035) and OS (HR = 0.36, p = 0.045). In vitro and in silico analyses confirmed that oxaliplatin has an anti-MCL cytotoxic effect that differs from that of other PD. R-DHAOx before ASCT provides better outcome in transplantation eligible young MCL patients.
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http://dx.doi.org/10.1038/s41409-020-01198-2DOI Listing
July 2021

Ambulatory high-dose methotrexate administration as central nervous system prophylaxis in patients with aggressive lymphoma.

Ann Hematol 2021 Apr 19;100(4):979-986. Epub 2021 Feb 19.

Service d'hémato-Oncologie, Assistance publique - Hôpitaux de Paris (AP-HP)- Hôpital Saint-Louis (SLS), 1, Avenue Claude Vellefaux, 75010, Paris, France.

High-dose methotrexate (HD-MTX) at 3 g/m is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.
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http://dx.doi.org/10.1007/s00277-020-04341-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960588PMC
April 2021

Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21).

Cold Spring Harb Mol Case Stud 2021 02 19;7(1). Epub 2021 Feb 19.

University of Burgundy-ISITE-BFC-Institut national de la santé et de la recherche médicale (Inserm) UMR1231, Faculty of Medicine, 21079 Dijon, France.

Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (), mutated , deletion 17p, and mutations in , (subclonal), and (subclonal). Quite strikingly, a novel mutation that was predicted to be loss of function was also seen. Exome sequencing identified, in addition, a potentially actionable mutation, together with novel somatic mutations affecting the homeobox transcription factor , known to control B-lymphocyte development and homing, and the epigenetic regulator , which is implicated in chromatin compaction and gene silencing. Neither nor mutations, predicted to be loss of function, have previously been reported in B-CLL. Sequencing confirmed the presence of these mutations together with , , and mutations, with the t(14;18)(q32;q21) translocation, in the initial diagnostic sample obtained 12 yr prior. This is suggestive of a role for these novel mutations in B-CLL initiation and stable clonal evolution, including upon treatment withdrawal. This case extends the spectrum of atypical B-CLL with t(14;18)(q32;q21) and highlights the value of more global precision genomics for patient follow-up and treatment in these patients.
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http://dx.doi.org/10.1101/mcs.a005934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903887PMC
February 2021

[New European Approvals: Brexucabtagene autoleucel for refractory mantle cell lymphoma after Bruton tyrosine kinase (BTK) inhibitor].

Bull Cancer 2021 Feb 30;108(2):142-144. Epub 2021 Jan 30.

Assistance Publique & Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Hémato-oncologie, Université de Paris, 1, avenue Claude Vellefaux, 75010 Paris, France.

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http://dx.doi.org/10.1016/j.bulcan.2020.12.006DOI Listing
February 2021

Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma.

Future Oncol 2021 Apr 2;17(11):1295-1310. Epub 2021 Feb 2.

Department of Haematology, Somogy County Kaposi Mór Hospital, Kaposvár, 7400, Hungary.

Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Treatment responders maintained higher FACT - Lymphoma (p ≤ 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.
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http://dx.doi.org/10.2217/fon-2020-0946DOI Listing
April 2021

Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older.

J Clin Oncol 2021 04 14;39(11):1203-1213. Epub 2021 Jan 14.

Department of Hematology, Centre Henri Becquerel, UNIROUEN, University of Normandy, INSERM U1245, Rouen, France.

Purpose: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy-cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)-is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non-germinal center B-cell-like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP.

Patients And Methods: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS).

Results: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP.

Conclusion: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.
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http://dx.doi.org/10.1200/JCO.20.02666DOI Listing
April 2021

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC].

Bull Cancer 2021 Jul-Aug;108(7-8):725-729. Epub 2021 Jan 7.

CHU de Lille, université Lille, Inserm U1286, Infinite, Lille, France.

The chimeric antigen receptor T-cells are a new class of anticancer treatment consisting in genetically modifying autologous or allogenic T-cells to make express a CAR directed against a membrane tumor antigen. In Europe, tisagenlecleucel (Kymriah) has a marketing authorization for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia in children and young adults and of R/R diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta) is the treatment of DLBCL and primary R/R mediastinal B-cell lymphoma. The two products are autologous T-cells directed against CD19. This collaborative work, part of a series of expert opinion-based work, aims to give practical advice to help centers in selection of patients for commercially available CAR T-cell treatment.
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http://dx.doi.org/10.1016/j.bulcan.2020.10.017DOI Listing
July 2021

Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis.

Blood Adv 2020 11;4(22):5773-5784

City of Hope National Medical Center, Duarte, CA.

Advanced marginal zone lymphoma (MZL) is an incurable B-cell malignancy dependent on B-cell receptor signaling. The phase 2 PCYC-1121 study demonstrated the safety and efficacy of single-agent ibrutinib 560 mg/d in 63 patients with relapsed/refractory MZL treated with prior rituximab (RTX) or rituximab-based chemoimmunotherapy (RTX-CIT). We report the final analysis of PCYC-1121 with median follow-up of 33.1 months (range: 1.4-44.6). Overall response rate (ORR) was 58%; median duration of response (DOR) was 27.6 months (95% confidence interval [CI]: 12.1 to not estimable [NE]); median progression-free survival (PFS) was 15.7 months (95% CI: 12.2-30.4); and median overall survival (OS) was not reached (95% CI: NE to NE). Patients with prior RTX treatment had better outcomes (ORR: 81%; median DOR: not reached [95% CI: 12.2 to NE]; median PFS: 30.4 months [95% CI: 22.1 to NE]; median OS: not reached [95% CI: 30.3 to NE]) vs those with prior RTX-CIT treatment (ORR: 51%; DOR: 12.4 months [95% CI: 2.8 to NE]; PFS: 13.8 months [95% CI: 8.3-22.5]; OS: not reached [95% CI: NE to NE]). ORRs were 63%, 47%, and 62% for extranodal, nodal, and splenic subtypes, respectively. With up to 45 months of ibrutinib treatment, the safety profile remained consistent with prior reports. The most common grade ≥3 event was anemia (16%). Exploratory biomarker analysis showed NF-κB pathway gene mutations correlated with outcomes. Final analysis of PCYC-1121 demonstrated long-term safety and efficacy of ibrutinib in patients with relapsed/refractory MZL, regardless of prior treatment or MZL subtype. This trial was registered at www.clinicaltrials.gov as #NCT01980628.
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http://dx.doi.org/10.1182/bloodadvances.2020003121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686907PMC
November 2020

Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA.

Blood 2021 Apr;137(17):2307-2320

Department of Hematology, University Hospital F. Mitterrand, Dijon, France; and.

Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.
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http://dx.doi.org/10.1182/blood.2020008750DOI Listing
April 2021

Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma.

Blood Adv 2020 11;4(22):5607-5615

Department of Hemato-Oncology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).
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http://dx.doi.org/10.1182/bloodadvances.2020003001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686887PMC
November 2020

Visceral leishmaniasis in patients with lymphoma: Case reports and review of the literature.

Medicine (Baltimore) 2020 Nov;99(45):e22787

Service de Dermatologie, APHP, Hôpital Saint Louis.

Introduction: Non-HIV-related visceral leishmaniasis (VL) is becoming increasingly prevalent in nontropical countries because of the increasing number of patients with chronic diseases and the development of immune-modulating drugs.

Patient Concerns: Case 1 is a 60-year-old male patient of Senegalese origin presented with weight loss, lymphadenopathy, anemia, and elevated lactate dehydrogenases. Case 2 is a 46-year-old male patient of Algerian origin, with a negative HIV serology presented with cutaneous lesions.

Diagnosis: Patient 1: The diagnosis of stage IV lymphocytic lymphoma (LL) was confirmed by an inguinal nodal biopsy in 2013. Patient 2: The diagnosis of T-cell lymphoma was made in 2003.

Interventions: Patient 1 received 5 cycles of bendamustine and rituximab followed by a complete remission. Patient 2 was initially treated with >10 different treatments followed by 8 different chemotherapy regimens due to the disease progression.

Outcomes: Patient 1: In 2017, after a follow-up of 4 years, the patient presented with fever, lymphadenopathy, splenomegaly, and pancytopenia in the setting of hemophagocytic syndrome. The initial diagnosis was a relapse of lymphoma and the patient was treated with ibrutinib. His status worsened, and Leishmania DNA was detected by polymerase chain reaction (PCR) on the blood and bone marrow aspirates. Ibrutinib was stopped. Amphotericin B treatment induced a complete clinical remission and clearance of Leishmania DNA from the blood.Patient 2: In 2017, after a follow-up of 14 years, the patient presented with fever, lymphadenopathy, hepatosplenomegaly, pancytopenia with hemophagocytic syndrome, and an increase in the tumor skin lesions. A skin biopsy was taken from the face and the patient. A careful reexamination of the skin biopsy revealed the presence of Leishmania bodies. He was treated with 40 mg/kg liposomal amphotericin B leading to a regression of the clinical symptoms and negativation of the blood PCR.

Conclusions: This case study shows that VL may be a diagnostic challenge in patients with lymphoma. Reactivation or primary infection should be considered in the differential diagnosis. The purpose of this study is to remind clinicians to think of VL in patients with systemic symptoms that could be misdiagnosed as a progression of the underlying lymphoma.
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http://dx.doi.org/10.1097/MD.0000000000022787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647553PMC
November 2020

Description of neurotoxicity in a series of patients treated with CAR T-cell therapy.

Sci Rep 2020 11 4;10(1):18997. Epub 2020 Nov 4.

Department of Neurology, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, 1 Avenue Claude Vellefaux, 75010, Paris, France.

Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1-2 severity and 34% had grade 3-4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3-4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.
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http://dx.doi.org/10.1038/s41598-020-76055-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642402PMC
November 2020

Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment.

Haematologica 2020 11 1;105(11):2592-2597. Epub 2020 Nov 1.

Division of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.

Early progression of disease (POD) within two years from diagnosis is linked with poor overall survival (OS) in follicular lymphoma but its prognostic role is less clear in extranodal marginal zone B-cell lymphoma (EMZL). We sought to identify prognostic factors associated with early POD and to determine whether is associated with inferior OS. We analyzed the impact of early POD in the IELSG19 clinical trial dataset (training set of 401 patients randomly assigned to chlorambucil or rituximab or chlorambucil plus rituximab). Reproducibility was examined in a validation set of 287 patients who received systemic treatment. In both sets, we excluded from the analysis the patients who, within 24 months from treatment start, died without progression or were lost to follow-up without prior progression. OS was calculated from progression in patients with early POD and from 24 months after start of treatment in those without (reference group). Early POD was observed in 69 of the 384 (18%) evaluable patients of the IELSG19 study. Patients with high-risk MALT-IPI were more likely to have early POD (p=0.006). The 10-year OS rate was 64% in the early POD group and 85% in the reference group (HR= 2.42, 95%CI, 1.35-4.34; log-rank P=0.002). This prognostic impact was confirmed in the validation set, in which early POD was observed in 64 out of 224 (29%) evaluable patients with 10-year OS rate of 48% in the early POD group and 71% in the reference group (HR= 2.15, 95%CI, 1.19-3.90; log-rank P=0.009). In patients with EMZL who received front-line systemic treatment, early POD is associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.
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http://dx.doi.org/10.3324/haematol.2019.237990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604574PMC
November 2020

Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study.

EClinicalMedicine 2020 Oct 13;27:100549. Epub 2020 Oct 13.

Service d'Hématologie Oncologie, Centre Hospitalier de Versailles, 177, rue de Versailles, 78157 Le Chesnay Cedex, France.

Background: Patients with lymphoma are immunocompromised because of the disease and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease 2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality.

Methods: This retrospective multicentric cohort study used the database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts.

Findings: Eighty-nine patients were included. The median age was 67 years (range, 19-92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62-81%). In multivariable analysis, having an age ≥ 70 years (hazard ratio 2·87, 1·20-6·85,  = 0·02) and relapsed/refractory lymphoma (hazard ratio 2·54, 1·14-5·66,  = 0·02) were associated with mortality. Recent bendamustine treatment ( = 9) was also pejorative (hazard ratio 3·20, 1·33-7·72,  = 0·01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients < 70 years of age without relapsed/refractory lymphoma was 88% (78% - 99%).

Interpretation: Thirty-day mortality was associated with being older and relapsed/refractory lymphoma. Survival of patients younger than 70 years without relapsed/refractory lymphoma was comparable to that of the general population.

Funding: There have been no specific funds to run this study.
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http://dx.doi.org/10.1016/j.eclinm.2020.100549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550257PMC
October 2020
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