Malignant non-Hodgkin Lymphoma Research Articles

Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines.

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 μM to 50 μM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.

Bilateral Malignant Non-Hodjkin's Lymphoma Metastatic of the Testis: A Case Report and Review of the Literature

Primary non-Hodgkin’s malignant lymphoma (NHML) of the testis is common in older men and is rare, accounting for between 1 and 9% of testicular tumors. The most common clinical manifestation is a painless unilateral testicular swelling but bilateral involvement is observed in about 35% of patients. We present a 61 year old patient with a history of right orchiectomy 7 months ago. He consulted us with a left testicular pain that was 4 months old. Clinical examination of the patient revealed a large hard left bursa and inguinal adenopathy. Given the patient’s history, the clinical picture, and the lack of additional immunostaining from the anatomical study, a further workup revealed a LMNH of high grade of metastatic germ cell type “B”. After RCP, the patient was refered to oncology.

Laryngeal Lymphoma: A Case Report

Primary laryngeal lymphoma is a rare entity, accounting for less than 1% of all primary laryngeal neoplasms. It is mainly primary non-Hodgkin's malignant lymphoma (NHLM). We report a new case in a 56-year-old woman who presented with progressive onset dysphonia [1]. Laryngoscopy revealed a budding lesion of the glotto-supglottic level (vocal cords, arytenoids, ventricular bands, epiglottis). Histology showed a peripheral T-cell lymphoma, CD3 and Ki67 positive, this pathology is difficult to diagnose, requires particular vigilance and should be managed according to current treatment trends for nodal LMNH.

Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma.

Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.

Testicular lymphoma: A case report

Primary testicular lymphoma (PTTL) is a rare and aggressive form of extraganglionic malignant non-Hodgkin's lymphoma (NML). It accounts for 1% of malignant non-Hodgkin's lymphomas, 2% of extranodal lymphomas and 5% of malignant testicular tumours. LTP is the most common form of testicular malignancy in men over 60. An enlarged inguinal orchiectomy should be performed for diagnostic and therapeutic purposes(1). Adjuvant treatment is based on systemic chemotherapy, administration of rituximab in the presence of CD20+ cells and intrathecal injection of methotrexate for neuro-meningeal prophylaxis. In this article, we report a case of testicular lymphoma in a 73-year-old patient who underwent inguinal orchiectomy followed by systemic and intrathecal CHOP chemotherapy.

A Unique Case of Large Pelvic Non-Hodgkin Lymphoma

Introduction: Non-Hodgkin lymphoma (NHL) represents a diverse group of malignancies arising from lymphocytes and lymphoid tissues. It encompasses multiple subtypes, including the aggressive diffuse large B-cell lymphoma (DLBCL), which is the most common type of NHL in adults. DLBCL typically presents as a rapidly growing mass in the lymph nodes or extranodal sites. While DLBCL can affect various regions of the body, its occurrence in the pelvic region is infrequent and poses unique diagnostic and therapeutic challenges. Case Description: We present a rare and intriguing case of a 51-year-old female admitted for acute on chronic microcytic anemia, with accompanying symptoms of decreased oral intake due to nausea, and vomiting, significant weight loss, night sweats, and lower quadrant abdominal pain. Additionally, she reported decreased urinary frequency, urgency. CT imaging of the abdomen and pelvis revealed a large soft tissue mass measuring 7.6 x 4.6 x 5.7 cm in the posterior right pelvic region, resulting in severe hydroureteronephrosis, along with bilateral iliac chain adenopathy, retroperitoneal lymph node enlargement, and severe splenomegaly. CT chest revealed several small lung nodules indicating distant metastasis. Additionally, the patient exhibited elevated levels of LDH, CA 199, and CRP, and decreased hemoglobin levels, indicating the presence of systemic disease. A CT-guided biopsy of the right pelvic mass confirmed the diagnosis of non-Hodgkin malignant lymphoma, specifically of the diffuse large B-cell type. Immunohistochemistry and flow cytometry demonstrated CD20 positivity in the proliferating large cells, consistent with DLBCL, and revealed a kappa-restricted B-cell population expressing CD19, CD20, and kappa surface immunoglobulin light chains. The PET scan showed prominent splenomegaly, adenopathy, and retroperitoneal involvement, corroborating the lymphoma diagnosis. The patient was discharged for outpatient follow-up with oncology with a treatment plan of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) administered every 3 weeks, omitting rituximab during the first cycle. Discussion: This case stands out due to the unusual presentation of a large DLBCL in the pelvic region, which is a relatively rare occurrence. The localization of DLBCL in the pelvis poses a diagnostic challenge, as symptoms may overlap with various other conditions. Moreover, the extensive involvement of the retroperitoneal lymph nodes and splenomegaly added complexity to the management of the disease. The rarity of DLBCL in the pelvis highlights the importance of considering lymphoma in the differential diagnosis of patients presenting with non-specific pelvic symptoms and acute anemia. Early recognition of such cases is crucial for timely intervention and optimal treatment planning. Understanding the immunophenotypic characteristics of the tumor is essential for tailoring effective therapeutic strategies. This unique case sheds light on the need for further research and evidence-based guidelines for managing NHL in uncommon anatomical locations, promoting better patient outcomes and quality of life.

Clinicopathological analysis and specific discriminating markers of interleukin detection in cerebrospinal fluid with primary central nervous system lymphoma: results from a retrospective study.

Primary central nervous system lymphoma (PCNSL) is special extranodal malignant non-Hodgkin lymphomas. This study analyzed clinical features and prognostic factors of PCNSL and evaluated the difference of interleukin (IL) concentrations incerebrospinal fluid (CSF) between PCNSL and systemic non-Hodgkin lymphoma (sNHL). Patients consecutive newly diagnosed with PCNSL were recruited, the demographic and clinicopathological data were retrospectively analyzed, and the potential prognostic factors for overall survival (OS) were identified with survival analysis. 27 patients with PCNSL and 21 patients with sNHL collected CSF IL-5, IL-6, and IL-10 concentrations at diagnosis. The difference in interleukin (IL) concentrations in two diseases was analyzed to evaluate the value of IL concentrations. A total of 64 patients with PCNSL were enrolled, the median age was 54.50years (range 16-85years); male: female ratio was 1.91. Headache was the most common complaint symptom involved in 42.19% (27/64) of patients. Diffuse large B-cell lymphoma (DLBCL) accounted for 89.06% (57/64) of patients; other uncommon types accounted for 3.13% (2/64). In prognostic analysis, multiple lesions and Ki67 ≥ 75% expression exhibited a worse prognosis(P = 0.041), and patients with autologous hematopoietic stem cell transplantation (auto-HSCT) treatment presented superior OS (P < 0.05). In multivariate analysis, BCL2 expression was revealed as an unfavorable prognostic marker, and auto-HSCT was revealed as a favorable prognostic marker. CSF IL-10 concentration in patients with PCNSL was significantly higher than sNHL (P = 0.000) and excluded other histopathology of NHL; IL-10 value was still significantly different between DLBCL of PCNSL and sDLBCL (P = 0.003). In ROC curve analysis, the cutoff value of IL-10 was 0.43pg/mL for the diagnosis value of PCNSL, sensitivity was 96.3%, specificity was 66.67%, and AUC was 0.84 (0.71-0.96). Although IL-6 concentration did not differ in the two groups, IL-10/IL-6 ratio was meaningful, with a cutoff value of 0.21, sensitivity of 81.48%, specificity of 80.95%, and AUC of 0.83 (0.71-0.95). This study highlights the characteristics of patients with PCNSL, potential prognostic makers also have been explained. CSF interleukin (IL) concentrations revealed IL-10 levels, and IL-10/IL-6 ratio may represent a useful biomarker in the differential diagnosis of PCNSL and sNHL.

BREAST LYMPHOMA

Primary breast lymphoma is a very rare histological entity of breast cancer. The Clinical and radiological aspects do not present any particular specificities. Diagnosis is often delayed. The treatment is mainly based on chemotherapy. We report the case of a patient with high grade malignant non-Hodgkin lymphoma. The symptomatology was made of breast swelling. The remote extension assessment was negative. The patient received 6 courses of type R mini CHOP chemotherapy followed by three-dimensional radiotherapy with a dose of 30 Gy in 15 fractions for 3 weeks. An echo mammography in between treatment showed: a partial response at 50%. Controle PET CT scan performed 3 weeks after the last cure having objectified: Complete disappearance of the active subcutaneous nodule at the level of the QSE of the right breast. Breast localisation of lymphoma is very rare. His prognosis was considerably improved due to a multidisciplinary approach.

Long Covid Case Report: Post SARS-CoV-2 Infection Evolution in Follicular Non-Hodgkin's Malignant Lymphoma, under Monoclonal Anti-CD20 Antibodies Treatment

Long Covid Case Report: Post SARS-CoV-2 Infection Evolution in Follicular Non-Hodgkin's Malignant Lymphoma, under Monoclonal Anti-CD20 Antibodies Treatment

FACIAL NERVE PARALYSIS AND INTUSSUSCEPTION AS CLINICAL PRESENTATIONS OF LYMPHOBLASTIC LYMPHOMA: A RARE PEDIATRIC CASE REPORT

Lymphoblastic lymphoma (LBL) is a highly aggressive lymphoblast neoplasm due to the presence of clonal hematopoietic stem cell abnormalities of B or T cell origin. LBL represents 30% of pediatric non-Hodgkin's lymphomas. We report a 2-year-11-month-old boy with complaints of a lump in the abdomen and facial paralysis on the left side. weight loss of 3 kg in 3 months, frequent nausea and vomiting, and constipation. On physical examination, the face was not symmetrical on the left and right. palpable mass from the right iliac region to the left iliac, measuring 17.5 x 10 x 5 cm, immobile, rubbery consistency. There is lymphadenopathy right inguinal region et sinistra. Abdominal ultrasound without contrast showed ileocolic intussusception, with histopathological results showing malignant non-Hodgkin's lymphoma. The therapy given was chemotherapy according to the protocol for non-Hodgkin's lymphoma. Facial nerve paralysis and intussusception are rare clinical features of LBL. It is important to consider a differential diagnosis such as LBL in a patient with a lump accompanied by facial nerve paralysis and intussusception. Histopathological and immunohistochemical examination were needed.Keywords: Â Lymphoblastic Lymphoma; Facial Nerve Paralysis; Intussusception

Primary Non-Hodgkin’s Lymphoma of the Breast: A Rare Case of Breast Location

Primary malignant lymphomas of the breast are rare, it represents less than 0.5% of all breast cancers. In this work we report an observation of primary non-Hodgkin malignant lymphoma of the breast with a review of the literature of epidemiological, clinical, histological and therapeutic aspects. Their clinical presentation is diverse. Imaging is non- specific, which can resemble all other types of breast cancer. The diagnosis can be evoked on cytological examination, its confirmation is always histological. The occurrence of non-Hodgkin malignant lymphoma requires a rigorous assessment of extension in the search for other primary localizations. Prognosis and treatment are similar to those of other lymphomatosis localizations.

The Role of the P-53 Gene and the p-53 Protein in the Oncogenesis of Non-Hodgkin's Malignant Lymphomas, Resistant to Conventional Oncological Treatments

The Role of the P-53 Gene and the p-53 Protein in the Oncogenesis of Non-Hodgkin's Malignant Lymphomas, Resistant to Conventional Oncological Treatments

Prebiotics for Chemotherapy-Induced Lower Intestinal Mucositis (CIM) With Moderate Protein Energy Malnutrition: A Case Report

ObjectivesChemotherapy-induced mucositis (CIM) is the most common side effect of chemotherapy. In addition, it reduces quality of life and leads to a reduction in chemotherapy doses, and eventually increasing mortality rate. CIM can cause malnutrition. Chemotherapy disrupts the symbiotic relationship between the microbiota and the patient. Various modalities are able to simulate colonization of probiotic bacteria in the intestine that have potential to be a strategy to restore healthy gut microbiota. Such as prebiotic.MethodsA 42-years old male with moderately malnourished (Subjective Global Assessment score B, Unintentional weight loss for 5 months (±7%) and body mass index was about 22.94 kg/m2) with diagnosis of Non-Hodgkin Malignant Lymphoma, Sinonasal Carcinoma and chemotherapy induced acute kidney injury. He had Leukopenia (2800/ul), decrease of kidney function (ureum/creatinine 28/1.5 mg/ul) and lymphopenia (926.8 ul).ResultsThe administration of nutrition therapy was initiated from 1000 kcal and increased gradually with total energy expenditure target of 2500 kcal via oral and parenteral nutrition, protein 1.2–1.5 g/Ideal Body Weight/day (15,3%) using high protein formula and amino acids parenteral nutrition. We administered prebiotics with a dose 5 gr/day for 6 weeks. Multivitamin, minerals and nutrition supplementations were administered; which were vitamin A, B1, B2, B6, B12, C, Folic acid, Zinc, Snakehead fish extract, Curcuma extract. During 13 days of nutritional therapy treatment, he achieved an average of 93,6% and 74% of energy and protein target, respectively. His clinical, functional capacity, laboratory were improved. Gastrointestinal symptoms such as nausea, vomiting, sore throat and constipation were improved and chemotherapy dose continued.ConclusionsClinical improvement such as increased oral intake after the prebiotics had given. Therefore, prebiotics had a potential benefit for CIM.Funding SourcesInstitutions from Department of Nutrition, Faculty of Medicine, Hasanuddin University.

Epidemiological, clinical and therapeutic aspects of chronic lymphoid hemopathies observed at the National Reference University Hospital Center (CHU-RN) of N Djamena

Aim. This study aimed to determine the epidemiological, clinical, therapeutic profile of chronic lymphoid hemopathies (CLH) and the viral factors linked to the genesis of HLCs at the CHU-RN of Ndjamena in Chad. Methods. A descriptive cross-sectional study over two and a half years, from October 2017 to March 2020 at the Hematology Unit of the National Reference University Hospital Center (CHU-RN) of Ndjamena. Were included patients in whom the diagnosis of chronic lymphoid hemopathy had been made. Results. Ninety-eight (98) cases of hematological malignancies were recorded out of 531 hematological consultations including 66 (12.43%) CLH and 67.35% of hematological malignancies with an annual incidence of 26.4 cases. Chronic lymphocytic leukemia (CLL) was 56.06% (n=37) followed by 25.76% (n=17) Malignant non-Hodgkin's lymphoma, 15.15% (n=10) Hodgkin's lymphoma and 3.03 % (n=2) cutaneous lymphoma. A male predominance was observed for all types of CLH. The most represented age groups were those of 51 to 60 years for CLL and 11 to 20 years for lymphomas. Conclusion: This study made it possible to have a better epidemiological knowledge and the viral factors related to the genesis of CLH at the CHU-RN of Ndjamena. It revealed difficulties in biological diagnosis and management, in particular the initiation of chemotherapy.

Diffuse large B-cell lymphoma-derived exosomes push macrophage polarization toward M2 phenotype via GP130/STAT3 signaling pathway

Growing evidence shows that cancer progression links with both heterogeneity of the tumor microenvironment and dysregulated activity of immune cells. Cancer-secreted exosomes are being recognized as indispensable mediators of the exchange cargo between cancer and immune cells. The M2-phenotype tumor-associated macrophages have the function of promoting tumor progression and drug resistance. Diffuse large B-cell lymphoma(DLBCL) is a highly heterogeneous and very common malignant non-Hodgkin's lymphoma. Here, we demonstrate that different subtype DLBCL cell-derived exosomes are internalized by macrophages, which can affect macrophages polarization.The mechanism of DLBCL-derived exosomes on macrophage polarization remains unclear currently. This study showed that DLBCL-secreted exosomes could induce the transformation of macrophages to a protumor M2-like phenotype, and block the drug-induced apoptosis of DLBCL cells in an indirect co-culture system. Different DLBCL-derived exosomes could change the phenotype of macrophages through the STAT3 signaling, which upregulated the expression of oncogenic genes and classical markers of M2-like phenotype macrophages, such as IL-10, CD206, and CD163. The addition of DLBCL-derived exosomes resulted in the activation of the STAT3 signaling pathway of M0/M2 macrophages in an indirect co-culture system. GP130 was highly enriched in DLBCL-derived exosomes, which triggered the activation of STAT3 of macrophages and subsequently induced the downstream targets such as BCL2, SURVIVIN, and BAX. The parallel changes of STAT3 and GP130 in macrophages confirmed that GP130 of DLBCL-derived exosomes promoted macrophage polarization by activating STAT3 signaling. Furthermore, all of these effects could be reversed by the GP130 inhibitor SC144. The data indicated that DLBCL-derived exosomes could trigger macrophages polarization into a pro-survival M2-like phenotype, which was at least partially through the GP130/STAT3 signaling pathway. Collectively, this study showed that DLBCL-derived exosomes could promote macrophages transformation to protumor M2-like phenotype in the tumor microenvironment.

A Review of Results from Clinical Trials Based on Co-Variants of the R-CHOP Regimen in Untreated Patients with Diffuse Large B-cell Lymphoma

Summary Since 2000, new drugs for treating lymphoproliferative diseases have been introduced in haematology, and their initial indications have been gradually expanded. Some of the so-called „target molecules“ have shown good efficacy when treating some malignant non-Hodgkin lymphomas. The possibility of achieving therapeutic disease control in some indolent non-Hodgkin lymphomas using drugs with a different mechanism of action from that of cytostatics has logically raised the question of a change in therapeutic management in other lymphoproliferative diseases. Since 2010, clinical trials have been initiated with untreated patients with aggressive non-Hodgkin‘s lymphoma - diffuse large B-cell lymphoma as the primary target. The key aim of most clinical trials has been to compare the efficacy of the so-called „gold standard“ - rituximab, cyclophosphamide, doxorubicin, oncovin, prednisolone (R- CHOP) versus its derivatives. The review discusses the results of completed clinical trials published on the Internet. These trials covered covariants of the R-CHOP regimen used as first-line treatment of patients with diffuse large B-cell lymphoma. The review also includes drugs registered in Bulgaria for the last ten years but with a different clinical indication at present. The results of five clinical trials in which obinotuzumab, venetoclax, lenalidomide, bortezomib, and ibrutinib were used are presented.

A case of primary intestinal lymphangiectasia with non-Hodgkin lymphoma

BackgroundPrimary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma.Case presentationA 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory.ConclusionOur report supports the hypothesis that PIL is associated with lymphoma development.

Diagnostic Difficulties and Management of Childhood Lymphoma: A Case Report

Primary dural lymphoma is a rare pathology, it is part of the malignant lymphoma of the central nervous system and it can reach the extradural or subdural space. We report a case of a little boy of three years and two months admitted to the Department of Neurosurgery CHU JRA for multiple swellings in the scalp associated with an altered general condition. The CT scan revealed a multiple extra-axial expansive process with retro-orbital extension responsible for an important exophthalmos as well as at the scalp level. Anatomopathological examination of the dura mater biopsy revealed a malignant non-Hodgkin's small cell lymphoma. The patient underwent chemotherapy of 05 sessions and the evolution was marked by the persistence of the symptoms. The post chemotherapy brain scan showed considerable extension of the lesions. The next step would be radiotherapy.

CLINICAL, IMAGING AND PATHOLOGICAL ASPECTS OF MAMMARY LYMPHOMAS SECONDARY TO MALIGNANT T- CELL CUTANEOUS LYMPHOMAS

Primary cutaneous lymphomas rank as the second most common clinical form of extranodal non-Hogdkin malignant lymphomas. Among non-Hodgkin malignant skin T-cell lymphomas, Mycosis Fungoides (MF) is the most frequent clinical occurence. The MF lymphoma originates in skin-homing helper T-cells, which express the CD4 + marker, showing chronic evolution, with recurrent lesions. In advanced stages, patients with Mycosis Fungoides may experience severe/extensive skin lesions or extracutaneous localizations of the disease. The secondary breast lymphoma is more common in non-Hodgkin malignant lymphoma than in Hodgkin lymphoma. Among the mammographic characteristics of breast lymphoma we mention: oval or round tumor mass, with well-defined or indistinct margins, absence of intratumoral calcifications, presence of intramammary lymph nodes, supra-adjacent skin thickening and lymphedema that causes diffuse increase in breast density. The ultrasound features of breast lymphoma run as follows: it is oval or round in shape, with well-defined or indistinct margins, which in Doppler ultrasound are identified as hypervascularized masses. The description of the imaging features of mammary lymphomas secondary to cutaneous T-cell lymphomas is required before performing the breast core-needle biopsy.

U.S. budget impact analysis of biosimilar versus originator intravenous rituximab for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

e18820 Background: Rituximab-abbs is an anti-CD20 monoclonal antibody and an important immuno-oncology agent for the treatment of B-cell malignancies NHL (diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma [FL]) and CLL. It is also indicated for patients with RA, GPA, and MPA. Rituximab-abbs was the first rituximab biosimilar approved in the US and is expected to reduce drug acquisition costs. This budget impact model (BIM) estimated the impact of replacing a share of originator rituximab (IV-R-REF) use with rituximab-abbs (IV-R-BIOSIM) for NHL (DLBCL and FL), CLL, RA, GPA, and MPA. The objective was to project incremental annual cost differences between IV-R-BIOSIM and IV-R-REF for a hypothetical 1-million-member US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated changes in 1-year drug and administration costs for an increased IV-R-BIOSIM uptake from 17.5% to 22.0%. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Dosing was based on a mean patient body surface area of 1.8 m2. Annual dose counts per patient were: 10 untreated FL with maintenance; 8 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 6 CLL, and 4 for RA, GPA, or MPA. All treatments were assumed to infuse over 3 hours. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was based on 2020 Medicare Part B 20% cost-share for office visits and drug products. Univariate sensitivity analyses were conducted. A scenario analysis was performed to project 2-year costs for extended FL maintenance treatment. Results: Estimated total annual plan incremental savings for a 1-million-member payer after the utilization shift were $312,379, equating to $0.31 per enrolled member per year (PMPY). Per-patient incremental drug cost savings with IV-R-BIOSIM for 1-year were $5,474–$12,924 (Table). The model was most sensitive to IV-R-REF cost and proportion of patients with RA. Conclusions: This analysis estimated annual savings of over $310,000 ($0.31 PMPY) for a 1-million-member US payer following a 4.5% utilization shift from IV-R-REF to IV-R-BIOSIM, demonstrating that IV-R-BIOSIM may confer considerable economic benefits vs originator rituximab.[Table: see text]