non-Hodgkin Lymphoma Patients Research Articles

G protein-coupled receptor 183 mediates the sensitization of Burkitt lymphoma tumors to CD47 immune checkpoint blockade by anti-CD20/PI3Kδi dual therapy.

Immunotherapy-based regimens have considerably improved the survival rate of B-cell non-Hodgkin lymphoma (B-NHL) patients in the last decades; however, most disease subtypes remain almost incurable. TG-1801, a bispecific antibody that targets CD47 selectively on CD19+ B-cells, is under clinical evaluation in relapsed/refractory (R/R) B-NHL patients either as a single-agent or in combination with ublituximab, a new generation CD20 antibody. A set of eight B-NHL cell lines and primary samples were cultured in vitro in the presence of bone marrow-derived stromal cells, M2-polarized primary macrophages, and primary circulating PBMCs as a source of effector cells. Cell response to TG-1801 alone or combined with the U2 regimen associating ublituximab to the PI3Kδ inhibitor umbralisib, was analyzed by proliferation assay, western blot, transcriptomic analysis (qPCR array and RNA sequencing followed by gene set enrichment analysis) and/or quantification of antibody-dependent cell death (ADCC) and antibody-dependent cell phagocytosis (ADCP). CRISPR-Cas9 gene edition was used to selectively abrogate GPR183 gene expression in B-NHL cells. In vivo, drug efficacy was determined in immunodeficient (NSG mice) or immune-competent (chicken embryo chorioallantoic membrane (CAM)) B-NHL xenograft models. Using a panel of B-NHL co-cultures, we show that TG-1801, by disrupting the CD47-SIRPα axis, potentiates anti-CD20-mediated ADCC and ADCP. This led to a remarkable and durable antitumor effect of the triplet therapy composed by TG-1801 and U2 regimen, in vitro, as well as in mice and CAM xenograft models of B-NHL. Transcriptomic analysis also uncovered the upregulation of the G protein-coupled and inflammatory receptor, GPR183, as a crucial event associated with the efficacy of the triplet combination. Genetic depletion and pharmacological inhibition of GPR183 impaired ADCP initiation, cytoskeleton remodeling and cell migration in 2D and 3D spheroid B-NHL co-cultures, and disrupted macrophage-mediated control of tumor growth in B-NHL CAM xenografts. Altogether, our results support a crucial role for GPR183 in the recognition and elimination of malignant B cells upon concomitant targeting of CD20, CD47 and PI3Kδ, and warrant further clinical evaluation of this triplet regimen in B-NHL.

A phase 1 first-in-human study of GS-0189, an anti-signal regulatory protein alpha (SIRPα) monoclonal antibody, in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent "don't eat me" signal for macrophages. Disruption of CD47-SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non-Hodgkin lymphoma (NHL) and other tumor types. GS-0189 is a novel anti-SIRPα humanized monoclonal antibody. Here we report: (1) clinical safety, preliminary activity, and pharmacokinetics of GS-0189 as monotherapy and in combination with rituximab from a phase 1 clinical trial in patients with relapsed/refractory NHL (NCT04502706, SRP001); (2) in vitro characterization of GS-0189 binding to SIRPα; and (3) in vitro phagocytic activity. Clinically, GS-0189 was well tolerated in patients with relapsed/refractory NHL with evidence of clinical activity in combination with rituximab. Receptor occupancy (RO) of GS-0189 was highly variable in NHL patients; binding affinity studies showed significantly higher affinity for SIRPα variant 1 than variant 2, consistent with RO in patient and healthy donor samples. In vitro phagocytosis induced by GS-0189 was also SIRPα variant-dependent. Although clinical development of GS-0189 was discontinued, the CD47-SIRPα signaling pathway remains a promising therapeutic target and should continue to be explored.

Abstract 993: Epigenetic immune cell profiling in B-non-Hodgkin lymphoma biopsies

Abstract Early detection and differential diagnosis of Non-Hodgkin lymphoma (NHL) is essential for the initiation of suitable therapy options. Biopsy based diagnosis allows allocation to World Health Organization (WHO) sub-classification groups but prognosis often needs identification of specific genetic aberrations or gene expression patterns. Despite this strategy, prognosis is difficult, since diseases, like e.g. mantel cell lymphoma, can be indolent or aggressive. Here we report the characterization of NHL biopsies using epigenetic immune cell quantification. This approach is based on the identification of specifically demethylated regions in individual immune cell types. These regions are then quantified using methylation-sensitive qPCR after bisulfite conversion. This highly reproducible and objective method allows in depth immunophenotyping of the tumor microenvironment. Next to CD4+ and CD8+ T cells, B cells and NK cells more specialized immune cells like regulatory T cells (Tregs), follicular T helper cells, PD-1 expressing cells and Myeloid derived suppressor cells (MDSC) were quantitatively determined in formalin-fixed tissue samples of 251 patients with different B cell Non-Hodgkin lymphomas. As a result, characteristic immune cell distribution patterns were identified for the different lymphoma entities, including chronic lymphocytic leukemia (B-CLL) (n=41), mantle cell lymphoma (MCL) (n=32), follicular lymphoma (FL) (n=33), diffuse large B cell lymphoma (DLBCL) (n=74), marginal zone lymphoma (MZL) (n=40) and B cell acute lymphoblastic leukemia (B-ALL) (n=26). In addition, substantial heterogeneity within the entities was observed that may correlate with disease prognosis. Among others, this is particularly the case for MDSC in B-CLL patients as well as for NK cells and Tregs in MCL and PD-1+ cells in FL patients. Currently clusters within the different disease groups are analyzed with regard to the clinical outcome to investigate if disease prognosis can be predicted by epigenetic immune cell quantification. In conclusion, epigenetic immune cell quantification is a suitable method to analyze the tumor microenvironment of NHL patients with the potential to support patient’s prognosis. Citation Format: Jeannette Werner, Steffi Walter, Christoph Sachsenmaier, Janika Schulze, Deborah Phippard, Sven Olek, Barbara Seliger, Claudia Wickenhauser. Epigenetic immune cell profiling in B-non-Hodgkin lymphoma biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 993.

Mobilization of Autologous Peripheral Blood Stem Cells (PBSC) in CD20+ Lymphoma Patients Using RICE, Granulocyte-Colony Stimulating Factor (G-CSF) and Plerixafor

RICE is salvage therapy for treating CD20+non-Hodgkin lymphoma (NHL). It is combined with G-CSF to collect autologous peripheral blood stem cells (aPBSC). Little data exists, though, on the combination of G-CSF and Plerixafor after RICE in mobilizing adequate number of CD34 cells and the product’s immune content. We report on the results of twenty CD20+ NHL patients after RICE, G-CSF and Plerixafor were given to collect aPBSC. The median number of cells collected was 12.92 × 10<sup>6</sup> CD34 cells/kg (range 5.44-83.76). Plerixafor toxicity included diarrhea (n = 5) and injection-site irritation (n = 1). Seventeen patients collected; fifteen patients did so in one session. Two patients with CLL/Richter or transformed follicular had positive-flow products. Addition of Plerixafor to G-CSF increased by 2.6-9 folds the number of blood CD34 cells. Sixteen patients went to ASCT, with a median of 7.29 × 10<sup>6</sup> CD34 cells/kg infused. The median engraftment time post-ASCT for neutrophils was 12 (range 10-19), for platelets ≥20K 11 (range 0-19) and ≥50K 16.5 (range 11-42) days. There were no graft failures. In APBSC product, there was no evidence of NK or LAK lytic activity (n = 10), only LAK activity (n = 4) and both LAK and NK activity (n = 2). Blood NK activity was common on day +28 post-ASCT. There was no significant correlation between apheresis product and the number of blood immune cells post- ASCT or relapse. Addition of Plerixafor to RICE/G-CSF is well tolerated. The majority of patients collected aPBSC in one session.

Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas.

Genetically modified T-cell immunotherapies are revolutionizing the therapeutic options for hematological malignancies, especially those of B-cell origin. Impressive efficacies of CD19-directed chimeric antigen receptor (CAR)-T therapy have been reported in refractory/relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL) patients who were resistant to current standard therapies, with a complete remission (CR) rate of approximately 50%. At the same time, problems of resistance and relapse following CAR-T therapy have drawn growing attention. Recently, great efforts have been made to determine various factors that are connected to the responses and outcomes following CAR-T therapy, which may not only allow us to recognize those with a higher likelihood of responding and who could benefit most from the therapy but also identify those with a high risk of resistance and relapse and to whom further appropriate treatment should be administered following CAR-T therapy. Thus, we concentrate on the biomarkers that can predict responses and outcomes after CD19-directed CAR-T immunotherapy. Furthermore, the mechanisms that may lead to treatment failure are also discussed in this review.

Bone marrow infiltration by Non-Hodgkin lymphoma: An experience in a tertiary care centre.

To determine the frequency and patterns of bone marrow infiltration in non-Hodgkin lymphoma patients. The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April to October 2021, and comprised patients of either gender aged 20-80 years who had been diagnosed with non-Hodgkin lymphoma. Following assessment and as per standard protocol, bone marrow aspirate and trephine biopsy were done on all patients from the posterior superior iliac spine, and slides were prepared and assessed. Data was analysed using SPSS 25. Of the 100 patients, 67(67%) were males and 33(33%) were females. The overall mean age was 54.99±12 years, and mean duration of symptoms was 11.7±1.5 months. Diffuse large B-cell lymphoma was the commonest type 43(43%). Infiltration of marrow occurred in 38(38%) patients, with 12(12%) of them being cases of mantle cell lymphoma. The commonest infiltration pattern was diffuse in 17(17%) cases, followed by focal/nodular in 10(10%). Diffuse large B-cell lymphoma was found to be the commonest type of non-Hodgkin lymphoma, and marrow infiltration occurred most frequently in cases of mantle cell lymphoma.

CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study.

To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. Forty-six patients were included in the study. The median age was 56.5years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.

Effects of Chemotherapy on Aortic 18-Fluorodeoxyglucose Uptake in Patients With Hodgkin and Non-Hodgkin Lymphoma

BackgroundDespite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). ObjectivesThe purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. MethodsBetween July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. ResultsPatients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = −0.20, 95% CI: −0.07 to −0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). ConclusionsAortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

Pediatric Non-Hodgkin Lymphoma: Ten-Year Experience with Berlin-Frankfurt-Munster (BFM) Protocols from a Tertiary Care Hospital in Turkey

Objective: Progress in therapy of childhood non-Hodgkin lymphoma (NHL) is one of the stunning success stories of the past two decades. In developed countries, more than 80% of children with NHL can now be cured with modern therapy, even patients with widely disseminated disease. The aim of this study is to analyze all NHL patients who were treated in a single tertiary center in Turkey. Methods: An analysis of data of children with NHL, diagnosed and treated between 2003 and 2012 according to the original Berlin-Frankfurt-Munster (BFM) protocol in Kocaeli University Pediatric Oncology Department was carried out. 
 Results: Forty-seven children were eligible for analysis. Mean age at diagnosis was 9.6 years with a male: female ratio of 1.9. Thirty-one patients (66%) were mature B-cell NHL with 23 patients (48.9%) Burkitt lymphoma, 7 patients (14.8%) diffuse large B-cell lymphoma, 1 patient (%2) primary mediastinal large B-cell lymphoma; 13 patients (27.6%) were lymphoblastic lymphoma with 11 patients (23.3%) T-lymphoblastic lymphoma and 2 patients (4.2%) B-lymphoblastic lymphoma, and also 3 patients (6.3%) were mature-T cell lymphoma-anaplastic large cell lymphoma. Four-year event-free survival was 78.7% and overall survival was 80.8%. 
 Conclusion: These results with BFM protocol administration reflect good treatment outcome in our patients.

The fusion oncogene VAV1-MYO1F triggers aberrant T-cell receptor signaling in vivo and drives peripheral T-cell lymphoma in mice.

VAV1-MYO1F is a recently identified gain-of-function fusion protein of the proto-oncogene Vav guanine nucleotide exchange factor 1 (VAV1) that is recurrently detected in T-cell non-Hodgkin's lymphoma (T-NHL) patients. However, the pathophysiological functions of VAV1-MYO1F in lymphomagenesis are insufficiently defined. Therefore, we generated transgenic mouse models to conditionally express VAV1-MYO1F in T-cells in vivo. We demonstrate that VAV1-MYO1F triggers cell autonomous activation of T-cell signaling with an activation of the ERK, JNK, and AKT pathways. VAV1-MYO1F expression induces a T-cell activation phenotype with high surface expression of CD25, ICOS, CD44, PD-1, and decreased CD62L as well as aberrant T-cell differentiation, proliferation, and neoplastic transformation. Consequently, the VAV1-MYO1F expressing T-cells induce a malignant T lymphoproliferative disease with 100% penetrance in vivo that mimics key aspects of human peripheral T-cell lymphoma. These results demonstrate that the human T-cell oncogene VAV1-MYO1F is sufficient to trigger oncogenic T-cell signaling and neoplastic transformation, and moreover, it provides a new clinically relevant mouse model to explore the pathogenesis of and treatment concepts for human T-cell lymphoma.

HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) predicts a high risk of hepatitis B reactivation in patients with B-cell lymphoma receiving rituximab based immunochemotherapy.

Patterns of hepatitis B virus reactivation (HBV-R) in HBsAg (-)/HBcAb (+) patients with B-cell non-Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (-)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV-R in HBsAg (-)/HBcAb (+) B-cell NHL patients was 6.3% (14/222), of which that in HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV-R in B-cell lymphoma patients (training phase hazard ratio[HR], 10.123; 95% confidence interval [CI], 3.389-30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684-205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529-33.207; p < 0.001). Inthetrainingcohort,the mortality rate of HBsAg (-)/HBcAb (+) B-cell NHL caused by HBV-R was 14.3% (2/14) while that for HBV reactivated HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV-R and high mortality after HBV-R was found in HBsAg (-)/HBsAb (-)/HBcAb (+)/HBeAg (-)/HBeAb (+) patients with B-cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.

Study on the Correlation between Elevated Serum Free Light Chain and Inferior Clinical Features or Hematological Parameters of Lymphoma Patients in Chengdu Area

To analyze the correlation of the serum free light chain elevated (sFLC) and clinical characteristics and hematological parameters of lymphoma in Chengdu area. 249 cases of non-Hodgkin lymphoma （NHL） out of 274 patients with lymphoma diagnosed in Sichuan People's Hospital from April 2019 to July 2021 were selected, the sFLC, clinical features and hematological parameters of the patients were analyzed retrospectively. The difference of clinical features between the patients with normal sFLC and elevated sFLC was examined by chi-square test. The difference of hematological parameters between patients with normal sFLC and elevated sFLC were examined by chi-square test and nonparametric Mann-Whitney U test. Among the 249 NHL patients, 55.42% （138/249） patients had an elevated sFLC, of which 9.24% （23/138） were being monoclonal and 46.18% （115/138） were polyclonal. The sFLC elevation was common in NHL, but varied according to the types of sFLC secretion （monoclonal or polyclonal）, and types of lymphoma. Furthermore, there were no significant statistical differences in clinical characteristics, including age, sex, stage disease, International Prognostic Index （IPI）, B symptoms, and bone marrow invasion between elevated sFLC and normal sFLC of the NHL patients （P＞0.05）. However, the patients with elevated sFLC had adverse hematological parameters more frequently, including higher WBC, ANC, AMC, hsCRP, Cr, Glb, LDH, and lower Hb, Alb. Elevated sFLC is associated with inferior hematological parameters, revealing the uniqueness of the diagnostic and prognostic value of sFLC in lymphoma in chengdu area.

Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma

To investigate the clinical efficacy and safety of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with lymphoma. The clinical data of 35 patients with lymphoma, including 5 patients of Hodgkin lymphoma and 30 patients of non-Hodgkin lymphoma, who underwent autologous stem cell transplantation after pretreatment with BeEAM regimen from January 2020 to June 2022 in Gansu Provincial Hospital were retrospectively analyzed. Hematopoietic reconstitution, disease outcome after transplantation and the side effects were analyzed. All 35 patients achieved hematopoietic reconstitution after AHSCT，the median time to neutrophil engraftment was 11 (8-15) days, and the median time to platelet engraftment was 12 (9-17) days. Among the 35 patients, 4 patients died at the end of follow-up, including 3 patients died of lymphoma recurrence or progression and 1 patient died of cerebral hemorrhage. Among 34 patients, 30 had no disease progression at the end of follow-up. The OS rates of patients at 12 and 24 months after transplantation were 90.97% and 90.97%, respectively. The 12 and 24 months PFS rates were 89.64% and 84.92%, respectively. Thiry-five patients underwent grade 3-4 bone marrow suppression. The non-hematological toxicity of BeEAM pretreatment regimen mainly included nausea, vomiting, diarrhea, and oral mucositis, 35 patients experienced nausea and vomiting, but only 4 patients had grade 3-4 nausea and vomiting. Eight patients experienced Grade 1-2 diarrhea. Oral mucositis occurred in 12 patients, including 1 patient of grade 3 oral mucositis. One patient with grade 3 oral mucositis also had grade 3-4 hypokalemia and hypon atremia. 8.6% of patients experienced Grade 1-2 abnormal liver and kidney function. An addition, infectious fever occurred in 18 patients during neutropenia. All patients improved after symptomatic treatment, and there were no transplant-related death. Bendamustine as a pretreatment regimen for autologous stem cell transplantation in lymphoma is effective, and the side effects are tolerable.

Fotemustine, etoposide, cytarabine, and cyclophosphamide (FEAC) conditioning regimen for autologous stem cell transplantation in lymphoma

To investigate the efficacy and safety of the FEAC (fotemustine, etoposide, cytarabine, and cyclophosphamide) conditioning regimen for the treatment of lymphoma, we retrospectively analyzed the records of 76 Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent autologous stem cell transplantation (ASCT) after the FEAC conditioning regimen. Their survival, as well as the clinical efficacy, hematopoietic engraftment time, and toxicity, were analyzed. One patient died of severe pulmonary infection, and the transplant-related mortality (TRM) was 1.3% (1/76). Hematopoietic engraftment was achieved successfully in the remaining 75 patients. The median times of neutrophil and platelet engraftment were 11 d (6–21 d) and 13 d (8–24 d), respectively. The 2-year progression-free survival (PFS) rate was 69.1%, and the 2-year overall survival (OS) rate was 84.2%. FEAC conditioning regimen has acceptable toxicity, and the prognosis of patients is good, making it a feasible alternative to the BEAM regimen for ASCT.

Characteristics of patients with hematologic malignancies without seroconversion post-COVID-19 third vaccine dosing.

The objective of this study is to explore the characteristics of the subset of patients with hematologic malignancies (HMs) who had little to no change in SARS-CoV-2 spike antibody index value levels after a third mRNA vaccine dose (3V) and to compare the cohort of patients who did and did not seroconvert post-3V to get a better understanding of the demographics and potential drivers of serostatus. This retrospective cohort study analyzed SARS-CoV-2 spike IgG antibody index values pre and post the 3V data on 625 patients diagnosed with HM across a large Midwestern United States healthcare system between 31 October 2019 and 31 January 2022. To assess the association between individual characteristics and seroconversion status, patients were placed into two groups based on IgG antibody status pre and post the 3V dose, (-/+) and (-/-). Odds ratios were used as measures of association for all categorical variables. Logistic regressions were used to measure the association between HM condition and seroconversion. HM diagnosis was significantly associated with seroconversion status (P = 0.0003) with patients non-Hodgkin lymphoma six times the odds of not seroconverting compared with multiple myeloma patients (P = 0.0010). Among the participants who were seronegative prior to 3V, 149 (55.6%) seroconverted after the 3V dose and 119 (44.4%) did not. This study focuses on an important subset of patients with HM who are not seroconverting after the COVID mRNA 3V. This gain in scientific knowledge is needed for clinicians to target and counsel these vulnerable patients.

Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.

Duvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies support the efficacy of duvelisib, the safety of duvelisib remains with great attention. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid neoplasm types. We searched prospective clinical trials from PUBMED, EMBASE, Cochrane Library, and ClinicalTrials.gov. For efficacy analysis, Overall response rate (ORR), complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), rate of progressive disease (PDR), median progression-free survival (mPFS), 12-/24-month PFS, and 12-month overall survival (OS) were assessed. For safety analysis, the incidences of any grade and grade ≥3 adverse events (AEs), serious AEs, and treatment-related discontinuation and death were evaluated. Subgroup analysis based on the disease type was performed. We included 11 studies and 683 patients, including 305 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 187 B-cell indolent non-Hodgkin lymphoma (iNHL), 39 B-cell aggressive non-Hodgkin lymphoma (aNHL), and 152 T-cell non-Hodgkin lymphoma (T-NHL) patients. The pooled ORR in CLL/SLL, iNHL, aNHL and T-NHL was 70%, 70%, 28% and 47%, respectively. Additionally, the pooled ORR in CLL/SLL patients with or without TP53 mutation/17p-deletion (62% vs. 74%, p=0.45) and in follicular lymphoma (FL) or other iNHL (69% vs. 57%, p=0.38) had no significant differences. Mantle cell lymphoma (MCL) patients had higher pooled ORR than other aNHL (68% vs. 17%, p=0.04). Angioimmunoblastic TCL (AITL) patients had higher pooled ORR than other PTCL patients (67% vs. 42%, p=0.01). The pooled incidence of any grade, grade ≥3, serious AEs, treatment-related discontinuation and death was 99%, 79%, 63%, 33% and 3%, respectively. The most frequent any-grade AEs were diarrhea (47%), ALT/AST increase (39%), and neutropenia (38%). The most frequent grade ≥3 AEs were neutropenia (25%), ALT/AST increased (16%), diarrhea (12%), and anemia (12%). Generally, duvelisib could offer favorable efficacy in patients with RR CLL/SLL, iNHL, MCL, and AITL. Risk and severity in duvelisib treatment may be mitigated through proper identification and management.

The impact of hepatitis B virus and hepatitis C virus infections in patients with Hodgkin's and non-Hodgkin's lymphoma.

This study aimed to determine the prevalence of HCV and occult HBV among newly diagnosed pre-treatment Egyptian lymphoma patients and evaluate patients' outcomes based on the presence of the viral infections. The study included 80 therapy-naïve lymphoma patients including 71 non-Hodgkin lymphoma (NHL) and 9 Hodgkin lymphoma disease (HD) in addition to 100 healthy volunteers. HBV screening using HBsAg and anti-HBc IgM and HCV using AB/Ag ELISA and real-time RT-PCR were screened in tested and control groups. The diagnosis was confirmed by histopathology. Overall survival (OS) and progression-free survival (PFS) were conducted to diseased patients. Healthy patients showed 4/100, (4%) active HCV infection and 1/100, (1%) active HBV infection and no occult HBV infection. Among NHL patients, 28 were positive for HBV (6 active and 22 occult HBV infection). Occult HBV was also detected in 5/9 HD patients. HCV was detected in (30/71, 42.3%) of NHL patients and in a single HD patient. Ten occult HBV NHL patients showed a mixed infection with HCV. The incidence of both HCV and HBV are higher in NHL than HL patients. After antitumor treatment, complete remission for lymphoma was achieved in 45% of patients. Both overall survival (OS) and progression-free survival (PFS) were correlated and significantly associated with patients' LDH levels. Our findings claim the suggestive role of HCV and occult HBV infections in NHL but not HL patients in comparison to healthy control, suggesting pre-screening of related factors including occult HBV in for potential better therapy response.

Semi-automated 18F-FDG PET segmentation methods for tumor volume determination in Non-Hodgkin lymphoma patients: a literature review, implementation and multi-threshold evaluation

In the treatment of Non-Hodgkin lymphoma (NHL), multiple therapeutic options are available. Improving outcome predictions are essential to optimize treatment. The metabolic active tumor volume (MATV) has shown to be a prognostic factor in NHL. It is usually retrieved using semi-automated thresholding methods based on standardized uptake values (SUV), calculated from 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) images. However, there is currently no consensus method for NHL. The aim of this study was to review literature on different segmentation methods used, and to evaluate selected methods by using an in house created software tool.A software tool, MUltiple SUV Threshold (MUST)-segmenter was developed where tumor locations are identified by placing seed-points on the PET images, followed by subsequent region growing. Based on a literature review, 9 SUV thresholding methods were selected and MATVs were extracted. The MUST-segmenter was utilized in a cohort of 68 patients with NHL. Differences in MATVs were assessed with paired t-tests, and correlations and distributions figures.High variability and significant differences between the MATVs based on different segmentation methods (p < 0.05) were observed in the NHL patients. Median MATVs ranged from 35 to 211 cc.No consensus for determining MATV is available based on the literature. Using the MUST-segmenter with 9 selected SUV thresholding methods, we demonstrated a large and significant variation in MATVs. Identifying the most optimal segmentation method for patients with NHL is essential to further improve predictions of toxicity, response, and treatment outcomes, which can be facilitated by the MUST-segmenter.

Therapy-related Acute Myeloid Leukemia in Non-Hodgkin Lymphoma Survivors: Risk, Survival Outcomes and Prognostic Factor Analysis.

Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. This extensive database study aims to quantify the risk of tAML in NHL and determine the impact of tAML on the overall survival (OS) of patients with NHL. Patients diagnosed with NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results database. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software were used to calculate SIR and the absolute excess risk of tAML. Overall survival (OS) was evaluated using Kaplan-Meier curves and compared using log-rank tests. Multivariate analysis was used to study the role of each covariate on OS in patients with tAML. The SIR of tAML was 4.89 (95% CI 4.41-5.41), with a higher incidence of tAML observed for age <60 years, NHL prior to 2013 and within 5 years of diagnosis, and those who received chemotherapy. NHL patients with tAML had lower OS than those without tAML (5-year OS 59% vs. 13%, p < 0.001). Patients with tAML showed worse OS than de novo AML in univariate analysis (5-year OS 13% vs. 25%, p = 0.001) but not in multivariate analysis (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years and lack of chemotherapy were associated with poor OS in tAML subcategory. Age, time since NHL diagnosis, and receipt of chemotherapy directly influence the risk of development of tAML in NHL survivors.

Extranodal Locatio of Lymphoma: Presentation and Evolutionary in Senegalese Patients

Introduction: The frequency of extranodal involvement in lymphoma is not rare, but variously described by authors in Africa. The objective of our work is to describe the profile of patients followed for lymphoma with extranodal locations. Methods: We conducted a descriptive, retrospective and analytic study at the clinical hematology department of Dalal Jamm Hospital, from September 2016 to June 2022. We included patients with a diagnosis of lymphoma immunohistochemistry, with extranodal involvement. The epidemiological, diagnostic, prognostic and survival aspects were studied. Results: Fifty-two (52) patients with extranodal localizations of their lymphoma were included. The mean age was 44.2 ± 17.6 years and the sex ratio was 1.2. The average time to diagnostic was 9.4 ± 3.6 months. We found a performance status ≥ 2 in 65.4% and at least one B symptom in 71.2% of cases. The extranodal manifestations were digestive (19%), cutaneous (17.5%), pleuropulmonary (17.5%), bone marrow (4.8%), thyroid (1.6%), parotid gland (1.6%) and breast (1.6%). Patients presented with Hodgkin’s lymphoma (HL) in 19.2% of cases and non-Hodgkin’s lymphoma (NHL) in 80.8% of cases. At the end of the extension checkup reviews, 61.5% were at an advanced stage and prognostic indices were unfavorable in 32% of patients. Conventional chemotherapy was conducted in 63.5% of patients of which 24 had NHL and 9 had HL. Immuno-chemoterapy was used in 26.9% of patients (13 cases of NHL, 1 case of HL). During the follow-up, we noted only 29.7% of complete remission. The median overall survival was 25.1 months [23.5 - 34.1 months] in HL group and 20.5 months [18.7 - 72.2 months] in NHL patients (p = 0.14). Conclusion: Our study shows that extranodal involvements of lymphomas are various, encountered more during NHL. In our practice, diagnosis is generally made at an advanced stage, with poor response to treatment.