Low-grade non-Hodgkin's Lymphoma Research Articles

P145 Single-centre experience of managing patients with anti-HMGCR antibody immune-mediated necrotizing myopathy

Abstract Background/Aims Anti-HMGCR antibodies are associated with a rare form of immune mediated necrotizing myopathy. Statin exposure is common, but statin-naïve presentations can occur. Given its rarity, optimal treatment regimes, alternative cholesterol lowering therapy, and implications of monitoring antibody titre have yet to be established. Methods A retrospective single-centre study was carried out at our tertiary neuromuscular clinic. All patients with a positive anti-HMGCR antibody presenting with a myopathy from 2010-2023, seen in the neuromuscular clinic at the Royal London Hospital, were included. Data on demographics, investigations, and treatments were recorded. Results In total, 39 patients were included in the analysis. Within the anti-HMGCR cohort, ethnically the largest proportion were white (27/39), followed by Asian (n = 7), and four patients black/black-African. 61% of patients were female. The commonest comorbidities were type 2 diabetes mellitus (67%), and hypertension (59%). Median age of onset was 66 (IQR 11). Three patients had no known statin exposure prior to disease onset, of which one had a limb-girdle muscular dystrophy distribution of muscle involvement. Median creatinine kinase (CK) at presentation was 8122 units/L (IQR 5338-14000). Alternative cholesterol lowering therapy was successfully commenced with ezetimibe (n = 18), or PCSK9 inhibitors (n = 3), with no progression of disease. Five malignancies were reported: one breast Ca, one tubo-ovarian, two thyroid, and one low grade NHL. None of the patients had cardiac involvement. 79% of patients were treated with prednisolone. Induction triple therapy of a steroid, IVIg and DMARD was used in 36% of patients. Methotrexate and IVIg were the commonest DMARDs used (59% and 54% respectively), often used in combination with prednisolone. Only four patients had a flare in disease requiring treatment re-escalation, nine patients are in remission off immunosuppression (Table 1). 21% were treated with rituximab, and two patients with abatacept. Where antibody titres were available, anti-HMGCR correlated significantly with CK levels (r = 0.689, p < 0.001). Of the patients with more than one HMGCR titre recorded, 8/14 reduced over time, and of those, 5/8 corresponded to a meaningful improvement in CK, while two patients had an improving CK, with a stable HMGCR titre. 4/14 patients are in remission off all immunosuppression, of which two of these had HMGCR titres below the threshold of positivity, and two had falling titres. Conclusion Anti-HMGCR IMNM remains rare. We demonstrate that remission off immunosuppression is achievable, and that anti-HMGCR titres may be of use to support immunosuppression withdrawal. We also show that, in this cohort of patients, alternative cholesterol lowering therapy is safe, and not associated with worsening disease. Disclosure K.E. Clark: None. R. Thomas: None. S. Kelly: None. L. Walker: None. A. Herrey: None. A. Dougan: None. R. Patel: None. S. Fhadil: None. A. Radunovic: None.

Head and Neck Lymphoma: Clinico-demographic Profile and Pattern of Presentations in a South Western Nigeria Tertiary Institution

Abstract
 Running title: A clinic-demographic profile and presentation of patient with head and neck lymphoma in a tertiary institution located in low-middle-income country.
 Introduction 
 Lymphoma is the second most common malignancy occurring in the head and neck region. It is broadly classified into Hodgkins lymphoma (HL) and non-Hodgkins lymphoma (NHL). It affects nodal and extra-nodal. The clinical presentation is largely determined by the anatomic distribution of the disease, clinical stage of the disease, age of the patients and presence of underlying diseases.
 Aims and Objectives
 This study aims to analyse the presentation of head and neck lymphomas over a fifteen years period at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife. The objectives include; to determine the prevalence and demographic indices (age and gender) of head and neck, document the histopathologic types, and determine the association between the anatomical sites and histopathologic subtypes of lymphomas
 Materials and Method
 This is a retrospective study among patients seen and diagnosed histologically with head and neck lymphomas between 2005 – 2019 at the departments of Oral Medicine and Pathology and Morbid Anatomy and Forensic Medicine, OAUTHC. Relevant record were retrieve from patient record and histological register from the hospital registry. Patients with incomplete data were excluded. The study was conducted in accordance with the Declaration of Helsinki, and approved by our institution Ethics Committee Board.
 Results 
 A total number of 54 cases of head and neck lymphoma were analysed with a prevalence of 30.9%. Out of the 54 cases, 46 were NHL and 8 cases were HL with a ratio of 5.8:1 respectively. A male preponderance was observed (M: F; 2.4:1). The lesion commonly affects patients in 3rd and 4th decade of life. All the histologic variants were seen to affect males more than females except for the unclassified variant of HL which affected both sexes equally. Low-grade and intermediate grade NHL affected the older patients more while high grade and miscellaneous subtypes affected the younger males. The cervical lymph nodes were the most common nodal site while the jaw was the most common extra-nodal site. Eighteen (39.1%) cases of NHL were diagnosed histological as miscellaneous while high and low grade had seven (15.2%) cases each.
 Conclusion
 Head and neck lymphoma remain relatively rare. One of every six lymphoma seen was HL, with male preponderance. High grade lymphoma is seen more in the younger patient. Lymphoma affect cervical lymph node more while jaw was the most common extranodal site. Obesity may be a predisposing factor in our environment but require future study to confirm.

Phase II Trial of Duvelisib Maintenance after Autologous Stem Cell Transplant in T-Cell and B-Cell Non-Hodgkin Lymphomas: Results of Safety Lead in

Introduction Duvelisib is a potent phosphoinositide-3-kinase delta (PI3K-δ) and gamma (PI3K-γ) inhibitor which has demonstrated efficacy in T-cell lymphomas (TCL) and low-grade B-cell Non-Hodgkin Lymphomas (B-NHL). It exerts its effect through inhibition of malignant cell proliferation and differentiation, as well as disruption of the tumor microenvironment. We aimed to evaluate the safety and efficacy of one year of duvelisib maintenance after consolidative autologous stem cell transplant (autoSCT) in patients with TCL and B-NHL. Methods Patients with TCL or B-NHL who received standard consolidative autoSCT began duvelisib maintenance after count recovery (approximately 30 days after transplant) and continued for 11 cycles (one year after transplant). Duvelisib started at 25 mg orally twice daily for two 28-day cycles (schedule 1), followed by 25 mg twice daily for 14 days on/ 14 days off (schedule 2) if the patient was in complete remission (CR) at day +100 or if intolerable toxicities developed. Patients in partial remission (PR) at day +100 continued schedule 1, and those with stable (SD) or progressive disease (PD) were taken off study. Results Twelve patients have been enrolled, starting in July 2020. Histologic subtypes were transformed follicular lymphoma (FL, n= 5), peripheral T-cell lymphoma (PTCL, n= 1), anaplastic large cell lymphoma (ALCL, n= 3), and angioimmunoblastic T-cell lymphoma (AITL, n= 3). Seven patients were male, median age was 62 (range, 25-71), and 10 patients had stage III/IV disease at diagnosis. Pre-transplant, 11 patients were in CR and 1 patient was in PR. Median follow-up was 23.7 months and median duration of duvelisib treatment was 8.7 months. Following enrollment of 7 patients, 2 patients developed grade 3 toxicities (elevated liver enzymes and diarrhea, respectively), prompting them to come off study. Patients were enrolled at schedule 2 thereafter, with subsequent improvement in tolerability. Most common adverse events (AEs) were hematologic, gastrointestinal, and hepatic (Table. 1). Grade 2-3 AEs probably related to treatment were seen in 6 patients: neutropenia (n= 2), lymphopenia (n= 1), diarrhea (n= 2), and elevated liver enzymes (AST/ALT) (n= 1). There were no grade 4-5 AEs and no deaths related to treatment. Permanent discontinuation of duvelisib due to grade 3 AEs occurred in 3 patients: elevated liver enzymes (AST/ALT), diarrhea, and lower extremity muscle weakness, respectively. The latter was deemed unlikely related to treatment and symptoms resolved upon follow-up. Of the 12 patients enrolled, 4 have relapsed (TCL, n= 2 and B-NHL, n= 2) and proceeded to additional treatment. All patients remain alive to date. Conclusions Duvelisib maintenance for up to one year after consolidative autoSCT in patients with TCL or B-NHL is safe and well tolerated at a dose schedule of 25 mg twice daily for 14 days on/ 14 days off, of 28-day cycles. Enrollment of patients undergoing consolidative autoSCT for TCL is ongoing to evaluate the efficacy of duvelisib maintenance.

Lymphoplasmacytic Lymphoma: An Atypical Presentation with IgG Monoclonal Gammopathy

Introduction Lymphocytic lymphoma (LPL) is a rare type of low-grade mature B-cell non-Hodgkin lymphoma, characterized by a monoclonal population of B lymphocytes, lymphoplasmacytic cells, and plasma cells. In around 95% of LPL cases, the serum immunoglobulin M (IgM) paraprotein is increased, which is correlated to Waldenstrom's Macroglobulinemia (WM), a clinicopathological disease. Only around 5% of LPL cases are associated with the serum paraproteins immunoglobulin G (IgG) or immunoglobulin A (IgA), or light chains alone, or are not linked to a paraprotein. Non-IgM LPLs have a wide range of clinical and pathological features, and MYD88 L265P mutations can occur, though at a lower frequency than WM. Hence, MYD88 testing is advised for prospective therapeutic purposes. Case Presentation A 69-year-old male was referred to a hematologist for uncontrolled epistaxis and periorbital edema. On initial workup, he had high total protein, elevated globulin, hypoalbuminemia, anemia, and proteinuria. Further investigation revealed a high IgG level with low IgM, IgA, and complement levels. Serum Protein Electrophoresis (SPEP): Increased total protein, decreased alpha two and beta globulins with a large monoclonal protein peak migrating in the gamma region, which accounts for 4.77 g/dl of the total 5.38g/dl gamma. Elevated Kappa Quantitative Free Light Chains of 355.39 (3.30 - 19.40mg/L), Decreased Lambda Quantitative Free Light Chains of 1.51 (5.71 - 26.30mg/L), Elevated Kappa Lambda Free Light Chains Ratio of 235.36 (0.26 - 1.65). Serum ImmunoFixation Electrophoresis demonstrated IgG-type kappa monoclonal protein with an additional faint band in IgG kappa. X-Ray skeletal survey showed a possible small lytic area in the inferior aspect of the C2 vertebral body, prompting him to have a cervical spine MRI which revealed no lytic lesions but an 18 mm vertebral body hemangioma inside T2. Molecular testing was positive for MYD88 Mutation c.794T>C (p. L265P) and negative for CXCR4 mutation. Plasma cell myeloma prognostic panel and chromosome analysis were normal. Flow cytometry of bone marrow aspirate showed a kappa light chain restricted plasma cell population (1.6% of total cells) with the following immunophenotype: positive for CD138, CD38, CD45, and negative for CD19, CD20, CD56, CD 117, and lambda light chains. The B-cell population showed kappa light chain restriction with the following immunophenotype: positive for CD19, CD20, and kappa light chains and negative for CD5, CD10, CD11c, CD23, and lambda light chains (Image 2). PET-CT of the whole body was negative for the extension of the disease. Transfusion with the two least incompatible PRBCs had little effect. However, plasmapheresis significantly improved his hemoglobin level by less than 7g/dl. A bone marrow biopsy revealed he had LPL with IgG Monoclonal Gammopathy (Image 1). He received one cycle of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone), followed by seven cycles of KCD (Carfilzomib, Cyclophosphamide, Dexamethasone) and Rituximab. The patient was diagnosed with low-grade B cell lymphoma with plasmocytic differentiation/lymphoplasmacytic lymphoma, with MYD88 mutation c.794T>C (p. L265P) positivity and CXCR4 mutation negativity. After plasmapheresis, the IgG level dropped to 1958. Follow-up SPEP revealed decreased alpha2 and beta globulins, decreased free lambda light chains, and increased K/L ratio. The patient was treated with Acalabrutinib, and his anemia, epistaxis, and coagulopathy resolved. Repeat PET-CT scan revealed no evidence of illness progression. Discussion LPL is not always linked with IgM monoclonal gammopathy; it can also be associated with IgG or IgA monoclonal gammopathy, light chains alone, or no monoclonal paraprotein. Non-IgM LPL has a high prevalence of extramedullary involvement, a lower rate of MYD88 mutation, and few hyper viscosity symptoms. The MYD88 mutation does not allow WM and Non-IgM LPL to be distinguished from other lymphoproliferative disorders with similar clinical and immunophenotypic features. The case described is unique as the patient has high levels of IgG (11,200) at presentation. In contrast to our patient, who has LPL with IgG Monoclonal gammopathy, approximately 95 percent of LPL patients have IgM Monoclonal gammopathy, which corresponds with WM. As a result, clinicians should be on the lookout for LPL that lacks an IgM Monoclonal Paraprotein.

Outcomes, Prognostic Factors, Predictors for Transformation to High-Grade B-Cell Lymphoma, and Therapeutic Management in Follicular Lymphoma: Real-World Evidence from a Large and Long-Term Latin-American Cohort

Introduction: Follicular lymphoma (FL) is the most common low-grade B-cell NHL, encompassing 20-25% of all NHLs. Although classically indolent, it has heterogeneous biological behavior and variable clinical outcomes. Histologic transformation (HT) to high-grade B-cell NHL compose its natural history, being associated with dismal survival. The therapeutic management of FL and its prognosis are highly dependent on its staging and tumor burden. Based on this premise, the present study aims to describe clinical-laboratory characteristics, assess outcomes, determine predictors of survival and HT, and compare responses between different therapeutic strategies applied in a large cohort of FL patients. Methods: This retrospective and single-center study involved 223 patients with FL grades 1-3A, diagnosed at the University of São Paulo, Brazil, from 2006 to 2022. FL patients were categorized into early-stage disease (I/II) (ES), advanced-stage (AS) (III/IV) with low tumor burden (LTV), and AS with high tumor burden (HTV) according to the GELF criteria. Endpoints included OS, PFS, early-relapse (< 24 months from diagnosis) and HT rates. Survival curves were constructed using the Kaplan-Meier method and the Log-Rank test was used to assess the relationship between variables and outcomes. Univariate analysis was performed using the Cox test and multivariate analysis by Cox regression method or proportional ratios model. The results were presented in HR and 95% CI, and a p-value ≤ 0.05 was considered statistically significant. Results: The median age at diagnosis was 60 years (30-98) and 54.8% (121/223) were female. Approximately 15% of cases (33/223) had ES, 18.4% (41/224) had AS-LTV, and 66.8% (149/223) had AS-HTV. BM involvement, leukemic presentation, splenomegaly, and serous effusions occurred in 48.9% (109/223), 11.7% (26/223), 12.6% (28/223), and 21.1% (47/223), respectively. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and involvement of ≥ 4 nodal areas were observed in 44.4% (99/223), 51.6% (115/223), 15.2% (34/223), and 56% (125/223), respectively - Table 1. Forty-nine percent of patients (110/223) were categorized as high-risk according to the FLIPI score. Table 2 summarizes the main outcomes and up-front therapeutic modalities applied in the whole cohort. With a median follow-up of 79.5 months (95% CI: 67.0-92.0) the OS medians were 18 years (95% CI: 14.9-21.1), 11 years (95% CI: 9.2-12.9), and 10.5 years (95% CI: 9.3-11.8) for ES, AS-LTV, and AS-HTV, respectively, p=0.138 Figure 1A. Similarly, the PFS medians were 6.7 years (95% CI: 3.6-9.8), 8.4 years (95% CI: 2.0-14.8), and 3.5 years (95 CI: 1.8-5.3) for ES, AS-LTV, and AS-HTV, respectively, p=0.171 Figure 1B. Early-relapses occurred in 36.3% (81/223) of cases, being 18.2% (6/33), 31.7% (13/41), and 41.0% (62/149) for ES, AS-LTV, and AS-HTV, respectively, p=0.032 Table 2. The overall mortality rate was 29.1% (65/223) for the whole cohort. HT was documented in 16.7% (37/223) of cases, being 3.0% (1/33), 14.6% (6/41) and 20.1% (30/149) for ES, AS-LTV, and AS-HTV, respectively, p=0.053 Table 2. Among patients with AS-HTV, the R-CHOP regimen did not promote increased OS compared to the R-CVP regimen (p=0.415), however it was associated with a substantial increase in PFS (p=0.005) Figure 2. Age ≥ 60 years (HR: 1.06, p<0.001), ≥ 2 comorbidities (HR: 3.85, p=0.014), B-symptoms (HR: 2.35, p=0.015), HT (HR: 2.77, p=0.002) and thrombocytopenia (HR: 2.96, p=0.028) were predictors of poor OS. Similarly, age ≥ 60 years (HR> 1.08, p<0.001), involvelment of ≥ 4 nodal areas (HR: 1.27, p<0.001), and high LDH levels (HR: 1.65, p=0.002) predicted decreased PFS. Additionally, serous effusions (HR: 2.09, p=0.05), albumin < 3.5 g/dL (HR: 2.82, p=0.05), B-symptoms (HR: 2.00, p=0.006), involvement of ≥ 4 nodal areas (HR: 1.21, p=0.014), and BM infiltration (HR: 2.11, p=0 .05) were the main predictors for HT. Conclusion: Although it is characteristically an indolent disease, our study demonstrated that a significant portion of FL patients have shortened survival. Here, we confirmed this prognostic heterogeneity, particularly considering the clinical staging and tumor burden. Therefore, FL patients with AS-HTV had higher HT rates and early-relapses, both classic adverse prognostic markers, as well as a tendency to higher mortality. We also identified clinical and laboratory predictors for HT, which may in a near future direct adapted-risk therapeutic strategies.

INNV-41. SUCCESSFUL TREATMENT OF EXTREMELY RARE CASE OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOPLASMACYTIC LYMPHOMA WITH BENDAMUSTINE-RITUXIMAB REGIMEN: A CASE REPORT

Abstract Lymphoplasmacytic lymphoma (LPL) is an uncommon low-grade non-Hodgkin B-cell lymphoma, with an annual incidence rate of 3 to 4 cases per million people. Primary central nervous system lymphoplasmacytic lymphoma (PCNSLPL) is even rarer, with fewer than 30 cases documented in the literature so far, to our knowledge. We report a case of a 40-year-old Caucasian male who presented with headaches and mild short-term memory problems. CT was suggestive of a right parietal mass. MRI revealed a right parietal homogeneously contrast-enhancing mass with T2 and flair changes extending to the right lateral ventricle, suggestive of vasogenic edema. An open biopsy was performed, and immunohistochemical analysis of the sample indicated lymphoplasmacytic lymphoma. PET scan was negative for hypermetabolic lesions. Bone marrow biopsy, serum protein electrophoresis, urine protein electrophoresis, and CSF analysis were unremarkable. A diagnosis of primary central nervous system lymphoplasmacytic lymphoma (PCNSLPL) was given after comprehensive workup. Treatment with 10 cycles of bendamustine and rituximab (BR regimen) resulted in a good response. The patient has been clinically stable and improving for over a year. Radiologically, there has been interval shrinkage of the right parietal mass and follow-up scans continue to be stable. The plan is to continue maintenance rituximab for 2 years. Although extremely rare, PCNSLPL should be considered in differential diagnoses of hematolymphoid tumors of the CNS and bendamustine with rituximab as induction treatment followed by maintenance rituximab might be considered.

Low Dose Involved Site Radiotherapy as Single Modality Treatment for Early-Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma.

Involved site radiotherapy as a single modality is considered standard of care for early-stage non-bulky nodular lymphocyte predominant Hodgkin's Lymphoma (NLPHL) with excellent rates of local control and overall survival. Guidelines suggest a dose of 30 Gy in conventional fractionation, however NLPHL has an indolent course and clinically behaves likes a low-grade lymphoma. Given the good prognosis NLPHL has been treated as low grade non-Hodgkin's lymphoma with a dose of 24 Gy in 12 fractions. Eleven patients with stage I-II non-bulky NLPHL treated with involved site radiotherapy alone to a dose of 24 Gy in 12 fractions between 2010 and 2021 were respectively identified and reviewed. Data on toxicity, post treatment PET, relapse and site of relapse were recorded from multidisciplinary meetings records and regular six monthly clinic reviews. Mean patient age was 45 (range 25-74), 9 were male. 8 were classified as having Ann-Arbor stage IA disease, and the remaining 3 had IIA disease. All patients were prescribed 24 Gy in 12 fractions, 6 patients had 3D-conformal radiotherapy, 1 static IMRT and 4 VMAT. After a median follow up of 32 months (range 12-147) the overall response rate was 100% and all patients had complete metabolic response on PET scan, performed three months following the completion of radiotherapy. All patients remained disease free throughout the follow up period (PFS and OS 100%). There were no late toxicities reported. This is the largest reported series of NLPHL patients treated with low dose involved site modern radiotherapy. Patients had excellent local control rates and survival with no significant toxicity, supporting the use of 24 Gy in early-stage non-bulky disease.

Experiences of and preferences for self-management among low grade non-Hodgkin's lymphoma survivors: A qualitative interview study

PurposeSupporting self-management is one strategy to help cancer survivors optimise their quality of life. Low grade non-Hodgkin's lymphoma is often incurable with a chronic disease trajectory requiring lifelong self-management. This study explored the views on self-management and preferences for self-management support among survivors of low grade non-Hodgkin's lymphoma and their informal caregivers more than 6 months after completion of systemic anti-cancer therapy. MethodIn-depth semi-structured telephone interviews were conducted. Key themes and subthemes were determined using inductive and deductive thematic analysis. ResultsThe sample included eight survivors of low grade non-Hodgkin's lymphoma and two family caregivers. There were four themes. 1) The chronic nature of low grade non-Hodgkin's lymphoma shapes perceptions of self-management; participants described their cancer as a chronic condition and self-management strategies reflected this. 2) Social networks enable self-management; participants emphasised the importance of making low grade non-Hodgkin's lymphoma survivors aware of social networks. 3) Support and monitoring are needed immediately after the initial treatment phase ends. 4) Preferred components of self-management support; this included regular review with monitoring, advice on diet, and strategies to manage the psychosocial consequences of low grade non-Hodgkin's lymphoma. ConclusionsProviding self-management support to those diagnosed with low grade non-Hodgkin's lymphoma is relevant given the chronic trajectory of the disease. Findings suggest that necessary components of a self-management support programme for those with low grade non-Hodgkin's lymphoma should include regular review with monitoring and practical support around facilitating engagement with social networks.

International validation of two EORTC questionnaires for assessment of health-related quality of life for patients with high-grade non-Hodgkin lymphoma (QLQ-NHL-HG29) and low-grade non-Hodgkin lymphoma (QLQ-NHL-LG20).

Health-related quality of life (HRQOL) is a critical aspect to consider when making treatment decisions for patients with non-Hodgkin-lymphoma (NHL). This international study by the European Organisation for Research and Treatment of Cancer (EORTC) tested the psychometric properties of two newly developed measures for patients with high-grade (HG)- and low-grade (LG)-NHL: the EORTC QLQ-NHL-HG29 and the EORTC QLQ-NHL-LG20 to supplement the core questionnaire (EORTC QLQ-C30). Overall, 768 patients with HG-NHL (N=423) and LG-NHL (N=345) from 12 countries completed the QLQ-C30, QLQ-NHL-HG29/QLQ-NHL-LG20 and a debriefing questionnaire at baseline, and a subset at follow-up for either retest (N=125/124) or responsiveness to change (RCA; N=98/49). Confirmatory factor analysis showed an acceptable to good fit of the 29 items of the QLQ-NHL-HG29 on its five scales (symptom burden [SB], neuropathy, physical condition/fatigue [PF], emotional impact [EI], and worries about health/functioning [WH]), and of the 20 items of the QLQ-NHL-LG20 on its four scales (SB, PF, EI, and WH). Completion took on average 10minutes. Test-retest reliability, convergent validity, known-group comparisons, and RCA find satisfactory results of both measures. A total of 31%-78% of patients with HG-NHL and 22%-73% of patients with LG-NHL reported symptoms and/or worries (e.g., tingling in hands/feet, lack of energy, and worries about recurrence). Patients reporting symptoms/worries had substantially lower HRQOL compared to those without. The use of the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20 questionnaires in clinical research and practice will provide clinically relevant data to better inform treatment decision-making. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed two questionnaires. These questionnaires measure health-related quality of life. The questionnaires are for patients with high-grade or low-grade non-Hodgkin lymphoma. They are called the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20. The questionnaires are now internationally validated. This study demonstrates that the questionnaires are reliably and valid, which are important aspects of a questionnaire. The questionnaires can now be used in clinical trials and practice. With the information gathered from the questionnaires, patients and clinicians can better evaluate treatments and discuss the best choice for a patient.

Real-world data from yttrium-90 ibritumomab tiuxetan treatment of relapsed or refractory indolent B-cell non-Hodgkin's lymphoma: J3Zi Study.

Yttrium-90 ibritumomab tiuxetan (90YIT) is a radioimmunotherapy agent in which the radioisotope yttrium-90 is bound to ibritumomab via tiuxetan as a chelating agent, and is used for relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma (rr-B-NHL). We conducted a joint study to evaluate the clinical outcome of 90YIT. The J3Zi study is composed of data from patients receiving 90YIT for rr-B-NHL from the top three institutions with 10years of 90YIT treatment experience from October 2008 to May 2018 in Japan. The efficacy, prognostic factors and safety of 90YIT were retrospectively evaluated. Data from 316 patients were analyzed; the mean age was 64.6years and the median number of prior treatments was 2. The median PFS was 3.0years, the final OS rate was over 60%, and the median OS was not reached during the study period. Significant factors influencing PFS were sIL-2R ≤ 500 (U/mL) and no disease progression within 24months of first treatment. Significant factors influencing OS were number of prior treatments ≤ 2 and sIL-2R ≤ 500 (U/mL). The PFS and OS rates were found to be significantly higher in the late half era (2013 to 2018) than in the early half era (2008 to 2013) during the study period. Prognosis following 90YIT treatment was improved in the late half era compared to the early half era. As treatment using 90YIT increased, administration of 90YIT shifted to the earlier treatment line. This may have contributed to the improvement of prognosis found in the late era. (UMIN000037105).

A RARE CASE OF PRIMARY PLEURAL LOW GRADE MARGINAL ZONE NONHODGKIN'S LYMPHOMA: A CASE REPORT

A primary pleural based marginal zone low grade NHL is very rare. Primary pleural Lymphomas account for less than 0.5% off all Non-Hodgkin Lymphomas and DLBCL is the most common subtype of primary pleural lymphomas. Here, we report a rare case of marginal zone lymphoma of low grade with Mib index of 15-20% presenting as a pleural based mass in a middle age individual. A 52 years old male presented with right sided pleural effusion with pleural thickening of soft tissue density. Thoracoscopy showed pleural based mass lesion and pleural biopsy revealed low grade marginal zone NHL which is very rare with very few cases documented till date. Diagnosis was based on Bcl-2 and CD20 marker positivity on IHC. Treatment of such Low-grade Marginal zone lymphoma is with Bendamustine and Rituximab.

Clinicopathological Spectrum of B-Cell Non-Hodgkin Lymphoma in Pakistan Population: A Single-Center Study.

Background B-cell non-Hodgkin lymphoma (NHL) is a common malignancy worldwide and in the Pakistani population. In our population, there was limited information regarding the clinicopathological characteristics of B-cell NHL. This study assessed the disease spectrum and most prevalent subtypes of B-cell NHL. Methodology An analysis of 548 cases was conducted in this cross-sectional study between January 2021 and September 2022, using a non-probability consecutive sampling approach. Patient age, gender, site of involvement, and diagnosis were documented according to the 5th edition of the World Health Organization (WHO)Classification of Tumors of Hematopoietic and Lymphoid Tissue, published in 2018. Data were entered and analyzed using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 26.0, Armonk, NY). Results The mean age of the patients was 47.73±20.44 years. There were 369 males (67.34%) and 179 females (32.66%). The most prevalent type of B-cell NHL was diffuse large B-cell lymphoma (DLBCL) (58.94%), followed by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (13.14%), Burkitt lymphoma (9.85%), and precursor B-cell lymphoblastic lymphoma (5.11%). In contrast to low-grade B-cell NHL (22.99%), high-grade B-cell NHL was more common (77.01%). Nodal involvement was observed in 62.04% of cases. The cervical region was the most common nodal site of involvement (62.04%), and the gastrointestinal tract (GIT) was the most common extranodal site (48.29%). Conclusion The incidence of B-cell NHL is higher in older age groups. The most common nodal site was the cervical region, whereas the extranodal site was the GIT. The most reported subtype was DLBCL, followed by CLL/SLL, and Burkitt lymphoma. The prevalence of high-grade B-cell NHL is higher than that of low-grade B-cell NHL.

Evaluation of Diagnostic Usefulness of CD200 Expression in B-cell Chronic Lymphoproliferative Disorders.

Immunophenotyping by flow cytometry (FCM) is a useful diagnostic tool for the evaluation of mature B-cell neoplasms (MBN). Here, CD200 expression may play a significant role and improve the distinction between various MBNs, but any potential as a prognostic marker is yet to be established. The present prospective study was conducted on all the suspected cases of MBNs. Immunophenotyping was done using a BD FACS Canto FCM using a panel of 4 to 6 color combinations of monoclonal antibodies; CD45, CD34, CD5, CD19, CD20, CD22, CD23, CD79b, FMC7, CD10, CD38, ZAP70, CD200, IgG, IgM, CD25, CD103, CD2, CD3, CD11c as well as κ and λ light chains. CD200 expression was compared in different subgroups. Of the total of 130 cases included in the study, CD200 was positive in 118 cases (90%). CD200 was expressed in 100% of the cases of CLL(86 cases), atypical CLL(06 cases), HCL(14 cases), FL(02 cases), SMZL(04 cases), LPL (01 case), and low-grade NHL (05 cases), with the highest intensity of fluorescence in HCL followed by CLL. All the cases of MCL and PLL were exclusively negative for CD200. In conclusion, the results of the present study support inclusion of this marker in the flow cytometric panels for the differential diagnosis of MBNs.

An An Overview of the Treatment of Non-Hodgkin Lymphoma with The Novel Cellular Therapies: CAR-T and Bispecific Monoclonal Antibodies

The management of non-Hodgkin lymphoma (NHL), including refractory and relapsed high grade and low-grade NHL has been significantly improved in recent years with the development of cellular therapies which harness the powerful anti-cancer effects of the immune system. These include the ground-breaking and now established technology of chimeric antigen receptor cell therapy as well as the promising new range of bispecific monoclonal antibody therapies. This article will give a summary of the currently available cellular and bi-specific antibody therapies for the treatment of NHL in licenced use and clinical trials, including an overview of their proven efficacy and characteristic side-effect profiles which distinguish them from conventional immunochemotherapy. The relative strengths and weaknesses of these comparable therapies will also be discussed together with consideration of where they may fit into the treatment sequence of NHL in the future. The article will also address the challenges of delivering these innovative technologies in different healthcare settings and how they may alter the future of therapy for patients with this form of cancer.

Ultra-low-dose radiotherapy in the treatment of ocular adnexal lymphoma: a prospective study

PurposeThis single-arm, prospective, exploratory study investigated the effectiveness of ultra-low-dose radiotherapy in the treatment of ocular adnexal lymphoma (OAL).Patients and methodsPatients with pathologically confirmed ocular adnexal low-grade non-Hodgkin lymphoma (predominantly mucosa-associated lymphoid tissue, MALT or follicular lymphoma) were included and treated with ultra-low-dose radiotherapy consisting of 2 successive fractions of 2 Gy at our institution between 2019 and 2021. Disease response was assessed clinically and radiographically within 4 months and at 3 to 6-month intervals after treatment. Data collected included rates of overall response, complete response (CR), partial response (PR), lesion size, and acute/chronic ocular toxic effects.ResultsSixteen patients with median age of 63 years (range 23–86 years) were included in the study. The histological subtypes included MALT (11 patients; 69%); follicular lymphoma (2 patients; 12%); Lymphoid hyperplasia (3 patient, 19%). At a median follow-up time of 15.5 months (range 5.0–30.0 months), the overall response rate was 88%, with a CR rate of 75% (n = 12) and a PR rate of 13% (n = 2). The average lesion area was reduced from 117.9 ± 60.4 mm2 before radiation therapy to 38.7 ± 46.0mm2 at initial evaluation post radiation therapy (P = 0.002, n = 16), and to 8.5 ± 21.2 mm2 (P < 0.001 compared with postoperative lesion area) in patients with response at one year (n = 11). Disease progression was noted in 2 patients (12%). The 1-year rates of local progression-free survivals (LPFS) and overall survival (OS) were 85% and 100%, respectively. No distant relapses were observed in any of the patients. No acute or late toxic effects were noted.ConclusionUltra–low-dose radiotherapy in patients with OAL is associated with excellent local disease control and long-term survival with no significant acute or late toxicities.

The Development of an Ontology Platform to Detect Serine Protease Involvement in COVID-19-Induced Co-Morbid BALT Lymphoma

Mucosal-associated lymphoid tissue (MALT) lymphoma is a rare, low-grade non-Hodgkin lymphoma that develops from B cells and often is diagnosed incidentally. Although it possesses diverse subvariants, such as bronchial-associated lymphoid tissue (BALT), its pathogenesis remains unclear. Currently, little consensus exists on a standard treatment approach partially due to their rare occurrences and heterogeneities, but also due to good prognosis. Studies over the past decades have identified an association between coronaviral infection and BALT formation, whereby mutations in serine proteases increase the risk of BALT lymphoma. The aim of this study was to use a computational approach to validate and further elucidate this relationship specifically between SARS-CoV-2 and BALT lymphoma development. To address this, ontologies for serine proteolytic homeostasis were constructed utilizing keywords and abstracts from PubMed, which were then used with parsing and logical "OR" functions to generate search inputs for the European Bioinformatics Institute (EBI) COVID-19 ontology and ClinicalTrials.gov (as in Table 1), specifically for and between "BALT", "lymphoma", "serine protease", and "heat shock protein" as a representative type of serine protease inhibitor (SerPIn) class. The Heat Shock Protein 70 family and its more specific subtype Binding immunoglobulin protein (BiP) (a.k.a. GRP-78, HSPA5, and Byun1), were also manually identified as an alternative results marker for efficacy comparison. Results showed that this approach successfully demonstrated a literary relationship between serine proteases (SERPINE1) with heat shock proteins (HS90) and COVID-19, with aryl hydrocarbon (Row 4 of Table 1) potentially acting as this bridge between BALT lymphomas, transmembrane bound serine proteases, and SARS-CoV-2. This demonstrates a viable approach to automate the development of future ontologies to detail the pathogenesis between SARS-CoV-2, BALT lymphoma, and serine proteases. However, it was limited in its ability to yield positive hit results for HSP70 or GRP-78, likely due to the narrow focus of the EBI COVID-19 ontology and PubMed for covering full text papers. Nonetheless, this platform still offers a wealth of genetic, proteomic, and clinical trials information that can effectively be deployed toward characterizing disease pathogenesis, even in rare hematological malignancies. Forward looking, future studies will continue to investigate the application of serine proteolytic homeostasis ontologies to BALT lymphoma to better characterize its pathogenesis and interplay with other malignancies, which can then be utilized to develop targeted therapeutic solutions for critical BALT and MALT malignancies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hepatitis C virus-associated B-cell lymphomas: The importance of the new direct antiviral agent therapy

Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus, responsible for both chronic hepatitis and extra-hepatic manifestations. Multiple epidemiologic, clinical, biological, and molecular studies have suggested that HCV plays a causal role also in the development of several lymphoproliferative disorders, either benign, such as mixed cryoglobulinemia, or malignant, such as B-cell non-Hodgkin lymphomas (NHL). Chronic viral antigenic stimulation of B-lymphocytes plays a fundamental basic role from the onset of lymphoma to its final steps. In the past, several studies demonstrated that the association of pegylated interferon plus ribavirin was able to eradicate HCV, with subsequent regression of indolent B-cell low-grade NHL. Other studies have demonstrated that direct antiviral agents (DAAs) therapy have some efficacy in HCV-associated NHL, particularly in patients with low-grade NHL or marginal zone-lymphoma, but these results need to be confirmed in larger studies with longer follow-up. The response rate of antiviral therapy seems favorable also in high grade NHL when DAAs therapy is administered in combination with chemotherapy and therefore antiviral therapy should be considered as a first-line approach in HCV-related NHL.

Comparison of baseline lymphoma and HIV characteristics in Malawi before and after implementation of universal antiretroviral therapy.

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.

CT features associated with underlying malignancy in patients with diagnosed mesenteric panniculitis

PurposeThe purpose of this study was to identify abdominal computed tomography (CT) features associated with underlying malignancy in patients with mesenteric panniculitis (MP). Materials and methodsThis single-institution retrospective longitudinal cohort study included patients with MP and a minimum 1-year abdominopelvic CT follow-up or 2-year clinical follow-up after initial abdominopelvic CT examination. Two radiologists, blinded to patients’ medical records, conjointly reviewed CT-based features of MP. Electronic medical records were reviewed for newly diagnosed malignancies with the following specific details: type (lymphoproliferative disease or solid malignancy), location (possible mesenteric drainage or distant), stage, time to diagnosis. An expert panel of three radiologists and one hemato-oncologist, who were blinded to the initial CT-based MP features, assessed the probability of association between MP and malignancy based on the malignancy characteristics. ResultsFrom 2006 to 2016, 444 patients with MP were included. There were 272 men and 172 women, with a median age of 64 years (age range: 25–89); the median overall follow-up was 36 months (IQR: 22, 60; range: 12–170). A total of 34 (8%) patients had a diagnosis of a new malignancy; 5 (1%) were considered possibly related to the MP, all being low-grade B-cell non-Hodgkin lymphomas. CT features associated with the presence of an underlying malignancy were the presence of an MP soft-tissue nodule with a short axis >10 mm (P < 0.0001) or lymphadenopathy in another abdominopelvic region (P < 0.0001). Associating these two features resulted in high diagnostic performance (sensitivity 100%; [95% CI: 57–100]; specificity 99% [95% CI: 98–100]). All related malignancies were identified. ConclusionFurther workup to rule out an underlying malignancy is only necessary in the presence of an MP soft-tissue nodule >10 mm or associated abdominopelvic lymphadenopathy.

Antibody Response to SARS-CoV-2 Vaccination in Patients With Lymphoproliferative Disorders and Plasma Cell Dyscrasias: Anti-Lymphoma Therapy as a Predictive Biomarker of Response to Vaccination.

We retrospectively analyzed SARS-CoV-2 vaccination antibody responses in a cohort of 273 patients with lymphoproliferative disorders or plasma cell dyscrasias who were seen at a single tertiary cancer center. Semi-quantitative anti-spike protein serologic testing was performed with enzyme immunoassay method. We found that the antibody response rate to SARS-CoV-2 vaccination was 74.7% in our patient cohort with no difference based on gender, age or race. The highest response rate was found in patients with Multiple Myeloma (MM) (95.5%). The response rates found in Diffuse Large B-Cell Lymphoma (DLBCL), Chronic Lymphocytic Leukemia (CLL), and Low-Grade Non-Hodgkin Lymphoma (LG-NHL) were 73.2%, 61.5% and 53% respectively. We also evaluated the effects of receiving active chemo-immunotherapy on SARS-CoV-2 vaccination antibody response. We found that the patients on treatment had lower response than the patients off treatment (62.1% versus 84.4% p<0.001). Thirty-four of 58 LG-NHL patients were receiving anti-lymphoma treatment with a lower SARS-CoV-2 vaccination response as compared to the patients who were not on treatment (29.4% v 87.5% p<0.001). We observed a similar pattern in CLL patients receiving treatment (48.1 v 76.0 p:0.049). We found that only disease type and treatment status (on-treatment vs. off- treatment), but not gender, age or race were significant predictors of non-response in the multivariable logistic regression model. The interaction between disease type and treatment status was not statistically significant by multivariate analysis. In conclusion, receiving anti-cancer treatment was found to play a significant role in decreasing the response to COVID-19 vaccination.