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Transfusion needs may impact patients' quality of life and CAR T-cells efficacy through transfusion-related immunomodulation. Transfusion needs after CD19 CAR T-cells for large B-cell lymphoma: predictive factors and impact on outcome. B Introduction: b Patients undergoing CAR T-cell therapy may experience severe cytopenias due to lymphodepleting chemotherapy and/or CAR T-cells. [Extracted from the article]

EARLY CTDNA CLEARANCE AFTER CAR T-CELL INFUSION PREDICTS OUTCOME IN PATIENTS WITH LARGE B-CELL LYMPHOMA: RESULTS FROM ALYCANTE, A PHASE 2 LYSA STUDY B Introduction: b CAR T-cells have significantly improved the outcome of patients with relapsed or refractory ( I R i / I R i ) large B-cell lymphoma (LBCL). The aim of our study was to monitor ctDNA before and after CAR T-cell infusion and correlate the results with clinical outcome in the ALYCANTE trial. [Extracted from the article]

Eligibility criteria include age 18-80y, lymphoma cell expression of either or both CD20 and CD22, and >= 2 prior treatment regimens including autologous CD19 CAR T-cell therapy if eligible. NATHALI-01: A PHASE 1/2A TRIAL OF UCART20X22, AN ALLOGENEIC DUAL CAR T-CELL THERAPY FOR PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (NHL) B Introduction: b Autologous CAR T-cell therapies have been transformative in the treatment of selected blood cancers. [Extracted from the article]

KILT: A RANDOMIZED NON-COMPARATIVE PHASE II LYSA STUDY OF LACUTAMAB WITH GEMOX VERSUS GEMOX IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA B Background: b Peripheral T-cell Lymphoma (PTCL) is a heterogeneous group of mature T-cell lymphomas (TCL) with adverse outcomes. KIR3DL2 is a killer immunoglobulin-like receptor that is expressed across different subtypes of TCL, including approximately 40% of PTCL. [Extracted from the article]

B Conclusions: b In the ALYCANTE study, axi-cel as second-line treatment in patients with LBCL who were not deemed candidates for HDCT/HSCT appears feasible and induces high response rates. The final analysis with 22 additional patients ( I n i = 62 vs. 40 patients at current cut-off) and a longer follow-up will be presented at the meeting, including subgroup analysis. B Introduction: b Patients with relapsed or refractory ( I R i / I R i ) large B-cell lymphoma (LBCL) after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options. [Extracted from the article]

Long term follow-up of untreated/relapsing MCL patients with the Ibrutinib, obinutuzumab, and venetoclax combination Two patients prematurely discontinued the treatment, one patient had a PD at C4 and has subsequently been treated with R-CHOP, one patient relapsed after treatment completion and has been treated with Glofitamab. B Backgrounds: b Targeted therapies (such as Ibrutinib and Venetoclax) have improved Mantle Cell Lymphoma (MCL) patients' outcomes. [Extracted from the article]

Regarding the B initial workup b , while at least one imagery was offered in 97% of patients, SP 18 sp FDG-PET/CT (EMZL 78%, SMZL 62%, NMZL 78%) was performed more frequently than CT-scan at baseline (EMZL 73%, SMZL 62%, NMZL 71%), although 47% patients underwent both procedures. Diagnosis of MZL was mostly evoked by general practitioners (48%) but patients were finally treated by hematologists (98%). B Background: b Marginal Zone Lymphomas (MZL) are a heterogeneous group of lymphomas that include three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). [Extracted from the article]

Background Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation ( HSCT). Chemotherapy leads to several side effects, with gastrointestinal ( GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. Aim To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. Methods We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. Results We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes ( P = 0.0002) and Actinobacteria ( P = 0.002) and significant increases in abundances of Proteobacteria ( P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism ( P = 0.0001), energy metabolism ( P = 0.001), metabolism of cofactors and vitamins ( P = 0.006), and increased capacity for glycan metabolism ( P = 0.0002), signal transduction ( P = 0.0002) and xenobiotics biodegradation ( P = 0.002). Conclusions Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal mucositis is defined as inflammation and/or ulcers of the gastrointestinal tract occurring as a complication of chemotherapy and radiation therapy, and affects about 50% of all cancer patients. Aim To assess the role of gut microbiota in the pathogenesis of gastrointestinal mucositis and the potential for manipulations of the microbiota to prevent and to treat mucositis. Methods Search of the literature published in English using Medline, Scopus and the Cochrane Library, with main search terms 'intestinal microbiota', 'bacteremia', 'mucositis', 'chemotherapy-induced diarrhoea', 'chemotherapy-induced mucositis', 'radiotherapy-induced mucositis'. Results The gut microbiota plays a major role in the maintenance of intestinal homoeostasis and integrity. Patients receiving cytotoxic and radiation therapy exhibit marked changes in intestinal microbiota, with most frequently, decrease in Bifidobacterium, Clostridium cluster XIVa, Faecalibacterium prausnitzii, and increase in Enterobacteriaceae and Bacteroides. These modifications may contribute to the development of mucositis, particularly diarrhoea and bacteraemia. The prevention of cancer therapy-induced mucositis by probiotics has been investigated in randomised clinical trials with some promising results. Three of six trials reported a significantly decreased incidence of diarrhoea. One trial reported a decrease in infectious complications. Conclusions The gut microbiota may play a major role in the pathogenesis of mucositis through the modification of intestinal barrier function, innate immunity and intestinal repair mechanisms. Better knowledge of these effects may lead to new therapeutic approaches and to the identification of predictive markers of mucositis. [ABSTRACT FROM AUTHOR]

Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1 year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67 years (range 28-96), and patients reported a favorable global health status (75/100 (IQR 58,83)) - which was higher in NMZL and lower in SMZL patients (p = 0.006). 18 FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

The presence of donor Vγ9Vδ2 T-cells after haploidentical hematopoietic stem cell transplant (h-HSCT) has been associated with improved disease-free survival. These cells kill tumor cells in a non-MHC restricted manner, do not induce graft-versus-host disease (GVHD), and can be generated by stimulation with zoledronic acid (ZA) in combination with interleukin-2 (IL-2). This monocentric phase I, open-label, dose-escalating study (ClinicalTrials.gov: NCT03862833) aimed at evaluating the safety and possibility to generate Vγ9Vδ2 T-cells early after h-HSCT. It applied a standard 3 + 3 protocol to determine the maximum tolerated dose (MTD) of increasing low-doses of IL-2 (5 days [d] per week, 4 weeks) in combination with a single dose of ZA, starting both the first Monday after d + 15 posttransplant. Vγ9Vδ2 T-cell monitoring was performed by multiparameter flow cytometry on blood samples and compared with a control cohort of h-HSCT recipients. Twenty-six patients were included between April 2019 and September 2022, 16 of whom being ultimately treated and seven being controls who received h-HSCT only. At the three dose levels tested, 1, 0, and 1 dose-limiting toxicities were observed. MTD was not reached. A significantly higher number of Vγ9Vδ2 T-cells was observed during IL-2 treatment compared with controls. In conclusion, early in vivo generation of Vγ9Vδ2 T-cells is feasible after h-HSCT by using a combination of ZA and repeated IL-2 infusions. This study paves the way to a future phase 2 study, with the hope to document lesser posttransplant relapse with this particular adaptive immunotherapy., (© 2024 Wiley Periodicals LLC.)

Very scarce data exist about outcomes of relapsed multiple myeloma patients who have failed proteasome inhibitor, immunomodulatory drug, anti-CD38 monoclonal antibody and therapies targeting B-cell maturation antigen (BCMA) (Quad-class exposed [QCE]). In this retrospective single-centre study, we determined progression-free survival (PFS) and overall survival (OS) from anti-BCMA failure in 45 QCE patients. Seven (16%) patients received antibody-drug conjugate, 20 (44%) bispecific antibodies and 18 (40%) CAR-T cell. Thirty patients (67%) received ≥1 subsequent line of treatment. PFS was 4.4 months (95% CI = 2.4-12.5) and OS 6.3 months (95% CI = 3.9-14.4). Having an adverse prognosis, QCE myeloma patients remain an unmet medical need., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m 2 /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m 2 and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy., (© 2018 Wiley Periodicals, Inc.)