Rituximab Maintenance Therapy in CD20+ B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4805-4805
Author(s):  
Sanja A. Trajkova ◽  
Lidija A. Cevreska ◽  
Irina Z. Panovska-Stavridis ◽  
Aleksandra Pivkova ◽  
Borce Georgievski ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Initial Treatment ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Pharmacokinetic Data ◽  
Rituximab Maintenance ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Purpose: Clinical and pharmacokinetic data suggest that high serum concentrations of rituximab and prolonged exposure to rituximab are associated with higher response rates and improved quality of response. We used rituximab-maintenance therapy to target minimal residual disease, with the aim of increasing the duration of remissions achieved following initial treatment. Methods: During 2001–2005, 14 patients with CD20+ B-cell non-Hodgkin’s lymphoma (seven with diffuse large B cell lymphoma [DLBCL] and seven with follicular lymphoma [FL]) were enrolled in the study. Patients with DLBCL and FL were required to have a CR or PR, respectively, following initial treatment. The most common initial treatments were R-CHOP, R-FC or CHOP. Rituximab-maintenance therapy was administered as 375mg/m2 doses every 3 months for 2 years. Three patients with aggressive DLBCL were treated with high-dose chemotherapy/autologous stem-cell transplantation (HDT/ASCT) and received rituximab-maintenance therapy every 2 months for four doses in total. Results: Most patients had disease of Ann Arbor stage ≥ 3 (two FL patients stage I). In patients with DLBCL, median event-free and overall survivals were 22.1 months and 22.3 months, respectively, with the corresponding values being 20.6 months and 26.1 months in patients with FL. To date, 13 patients are in continuous clinical remission and only one patient has relapsed. Conclusions: Rituximab-maintenance therapy is effective and well tolerated in this setting. Recruitment for this study is ongoing and evaluation of a larger patient population, together with a longer follow-up, will determine whether this treatment approach has curative potential.

scholarly journals Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin’s lymphoma

2021 ◽  
Vol 9 (2) ◽  
pp. e002097
Author(s):  
Kathryn Lurain ◽  
Ramya Ramaswami ◽  
Ralph Mangusan ◽  
Anaida Widell ◽  
Irene Ekwede ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hiv And Aids ◽  
Hodgkin's Lymphoma ◽  
People Living With Hiv ◽  
Oncogenic Viruses ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

BackgroundNon-Hodgkin’s lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.MethodsWe conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.ResultsWe identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1–21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2–3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.ConclusionsTreatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

scholarly journals Case of extranodal non-hodgkins lymphoma involving the endometrium and the ovaries: a rare case report

2017 ◽  
Vol 6 (9) ◽  
pp. 4131 ◽  
Author(s):  
Lakshmi Manjeera Malempati ◽  
Neetha Nandan ◽  
Sagarika Babu
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Female Genital Tract ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Western World ◽  
Non Hodgkin’S Lymphoma ◽  
Uterine Neoplasm ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Non-Hodgkin’s lymphoma(NHL) is most commonly encountered during childhood and rarely among the adults. Primary malignant lymphoma in the female genital tract are rare Moreover they present with non-specific symptoms and hence there may be delay in the diagnosis. It is difficult to distinguish this condition from the more common uterine neoplasm such as uterine fibroids or sarcoma. Diffuse large B-cell lymphoma (DLBCL) is most commonly seen among the cases of NHL, contributing to among one third of NHL in the western world. DLBCL is common in elderly population. A 69-year-old postmenopausal woman who came with watery discharge since, 15 days was evaluated clinically and radiologically and was found to have thickened endometrium and enlarged ovaries, for which endometrial biopsy was taken that showed non-secretory endometrium with atrophic changes. Tumor markers found to be normal. TAH+BSO was done and the histopathology showed Non-Hodgkin’s lymphoma, diffuse large B cell type of the endometrium and both ovaries which was confirmed by immune histochemical marker study. PET-CT was done that showed metabolically active para aortic and common iliac lymph nodes thereby she was diagnosed with stage II (Ann Arbor Staging) non-Hodgkin’s lymphoma, hence she received 6 cycles of R-CHOP. As evident in our case, non-Hodgkin’s Lymphoma of the endometrium and the ovaries being an extremely rare condition, high-degree of suspicion is required for its prompt diagnosis and treatment.

CERA (Continuous Erythropoietin Receptor Activator): Dose-Response Trial of Subcutaneous (SC) Administration Once Every 3 Weeks (Q3W) to Patients with Aggressive Non-Hodgkin’s Lymphoma and Anemia Receiving Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4225-4225 ◽  
Author(s):  
Anders Osterborg ◽  
Andrzej Hellmann ◽  
Stephen Couban
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Dose Response ◽  
Combination Chemotherapy ◽  
Hodgkin’S Lymphoma ◽  
Transferrin Saturation ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract CERA is an erythropoiesis-stimulating agent (ESA) acting differently at the receptor level with a prolonged half-life. In this ongoing, multicenter, randomized, open-label, Phase II dose-response study, CERA was administered subcutaneously in a Q3W schedule to 93 transfusion-independent patients with aggressive (intermediate or high grade) B-cell non-Hodgkin’s lymphoma (NHL) and anemia receiving combination chemotherapy. Eligible patients met the following inclusion criteria: age ≥18 years, hemoglobin (Hb) <11 g/dL, combination chemotherapy scheduled to be administered throughout the 12-week treatment period, life expectancy >6 months, and Eastern Cooperative Oncology Group (ECOG) performance status grade 0–2. Major exclusion criteria included transferrin saturation <20% and platelet count <50 x 109/L. No patient had received an ESA in the 8 weeks prior to the first dose of CERA. Patients were randomized to receive CERA 2.1 μg/kg (n=31), 4.2 μg/kg (n=30), or 6.3 μg/kg (n=32) administered once every 3 weeks for 12 weeks. The primary efficacy variable was time-adjusted average change in Hb from baseline during 12 weeks, until end of initial treatment (last observed value before dose change or transfusion). Enrollment has been completed; the treatment phase of the trial is nearing conclusion. Demographics show similar baseline characteristics in all three patient subgroups [mean age: 62.9 years (2.1 μg/kg); 59.1 years (4.2 μg/kg); 64.3 years (6.3 μg/kg)]. Diffuse large B-cell lymphoma was the most common lymphoma in all three subgroups (87%, 70%, and 84% of patients in the 2.1, 4.2, and 6.3 μg/kg subgroups, respectively). To date, the majority of patients receive an anthracycline-containing chemotherapy regimen, either standard CHOP or CHOP plus rituximab. Preliminary efficacy and safety results will be presented. Ongoing assessments have indicated a safety profile consistent with that seen in patients with aggressive NHL and anemia receiving chemotherapy. This Phase II trial will help further characterize the ability of CERA to safely correct anemia when administered at an extended dosing interval (Q3W) to patients with aggressive NHL receiving chemotherapy.

Preclinical Safety and Efficacy of Two Novel Immunotoxins Consisting of Ranpirnase (Rap) Fused to an Internalizing Anti-CD74 Humanized IgG4 Antibody in Human Non-Hodgkin’s Lymphoma Xenografts.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 346-346 ◽  
Author(s):  
Puja Sapra ◽  
Chien-Hsing Chang ◽  
Sailaja Vanama ◽  
Sharon Singh ◽  
Hans J. Hansen ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Specific Binding ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Therapeutic Effects ◽  
Single Chain ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Recombinant Immunotoxins

Abstract Rap, an amphibian ribonuclease, is a single-chain protein of 104 amino acids that kills cells by degrading t-RNA upon internalization. CD74 is a rapidly internalizing type-II transmembrane chaperone molecule associated with HLA-DR, and has high expression on hematological malignancies including B-cell non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). We have constructed and evaluated two novel immunotoxins, 2L-Rap-hLL1-γ 4P and 2L-Rap(N69Q)-hLL1-γ 4P, each composed of two Rap molecules fused to hLL1, an internalizing anti-CD74 humanized monoclonal antibody. The Rap gene was inserted at the N-terminus of the light chain in the expression vector of hLL1 and expressed in NS0 mouse myeloma cells. To reduce unwanted cytotoxicity, the CH1, CH2, CH3 and the hinge regions of the γ 1 chain of hLL1 were replaced with those of γ 4. Additionally, the serine residue in the hinge region was converted to proline to prevent the formation of IgG4 half-molecules. Noting that Rap contains a potential N-glycosylation site at the 69th residue of asparagine(N69), a variant of Rap, referred to as Rap(N69Q), was constructed by changing N to Q (glutamine) and this variant was used to make 2L-Rap(N69Q)-hLL1-γ 4P. Purified recombinant immunotoxins were shown to be a single peak by SE-HPLC and their MW determined by MALDI-TOF to be 177,150, which is in agreement with the MW of one IgG (150,000) plus two Rap molecules (24,000). In vitro, both immunotoxins retained RNase activity, specific binding to CD74, and were significantly more potent against CD74-positive NHL and MM cell lines (Daudi, Raji and MC/CAR) than naked hLL1 or non-specific control immunotoxin, 2L-Rap(N69Q)-hRS7(immunotoxin against EGP-1). In Raji and Daudi Burkitt’s lymphoma xenograft models, treatment with a single 5- to 50-μg dose of 2L-Rap-hLL1-γ 4P, given as early or delayed treatment, resulted in cures of most animals. Additionally, treatment with a single 15-μg dose of 2L-Rap(N69Q)-hLL1-γ 4P 1-day post injection of cells resulted in 100% cures. Treatment with 2L-Rap-hLL1-γ 4P or 2L-Rap(N69Q)-hLL1-γ 4P was significantly better than all controls, including saline, naked hLL1 and non-specific immunotoxin. The maximum tolerated dose of 2L-Rap-hLL1-γ 4P or 2L-Rap(N69Q)-hLL1-γ 4P in SCID or BALB/c mice was 50 μg/mouse and the dose-limiting toxicity was hepatic. In our preliminary studies, we have observed that treating animals with NSAID’s, such as indomethacin, can ameliorate the hepatoxicity of 2L-Rap-hLL1-γ 4P. All animals that were injected with 100 μg/mouse 2L-Rap-hLL1-γ 4P alone died with a median survival time of 7 days; however, animals treated with 1.25mg/kg indomethacin prior and post-treatment of 2L-Rap-hLL1-γ 4P survived the duration of study (day 40). Experiments to determine the possible causes of liver toxicity produced by 2L-Rap-hLL1-γ 4P and to determine the MTD of Rap-immunotoxins in mice after treatment with indomethacin are ongoing. In conclusion, we have constructed two CD74-targeted novel recombinant immunotoxins containing Rap molecules that have demonstrated curative therapeutic effects in animal models of human B-cell lymphoma, and thus could be potential therapeutics for CD74-postive lymphomas and myelomas.

Clinical Features and Prognostic Relevance of Ovarian Involvement in Non-Hodgkin's Lymphoma: a Consortium for Improving Survival of Lymphoma (CISL) Report.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4999-4999
Author(s):  
Jina Yoon ◽  
Seok Jin Kim ◽  
Jong Ho Won ◽  
Chul Won Choi ◽  
Hyeon-Seok Eom ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Disseminated Disease ◽  
Ovarian Involvement

Abstract Abstract 4999 Introduction Ovary can be involved as a primary ovarian lymphoma or secondarily involved by disseminated disease of non-Hodgkin's lymphoma. However, ovarian involvement is an extremely rare event in non-Hodgkin's lymphoma. Thus, it clinical features and prognostic relevance has rarely been addressed, and most publications refer to a single or a few cases. Thus, we retrospectively analyzed patients with ovarian involvement Patients and methods 32 patients with ovarian involvement were assembled from 8 hospitals affiliated with the CISL (Consortium for Improving Survival of Lymphoma), a Korean lymphoma study group. Primary ovarian involvement was defined as a lymphoma confined to ovary with or without involvement of adjacent lymph nodes and contiguous organs. Secondary ovarian lymphoma was defined as a secondary involvement of ovary in disseminated disease of lymphoma at initial diagnosis. Results Twelve patients had primary ovarian lymphoma (37.5%) while twenty patients (62.5%) had secondary ovarian involvement by systemic disease. The clinical manifestations of ovarian involvement were similar to that of other ovarian tumors, namely an abdominal pain (31%), abdominal distension (19%) or lower abdominal palpable mass (16%). Pathological review according to the WHO classification showed that the most common histological subtype was diffuse large B-cell lymphoma (DLBCL, 75.0%, 24/32), and the frequency of other subtypes was as follows: Burkitt lymphoma (BL, 12.5%, 4/32), lymphoblastic lymphoma (6.3%, 2/32), marginal zone B-cell lymphoma (MZL, 3.1%, 1/32), peripheral T-cell lymphoma, unspecified (PTCL-U, 3.1%, 1/32). The median age (43 years, range 18-80) was younger than that of previously reported other organs such as uterus or prostate. The presence of B symptoms was only observed in 31.3%, and the performance status was good (84.4% of patients had less than grade II of ECOG performance status). The cases involving two or more than two extranodal sites were 68.8% while cases with elevated level of serum LDH were 59.4%. Thus, 59.4% of patients had the low or low-intermediate score of IPI score. Bilateral ovarian involvement was found in 12/32 (38%) while unilateral involvement was 20/32 (63%, 9 right and 11 left side. Three patients showed the involvement of central nervous system (CNS) at diagnosis (3/32, 9.4%). These three patients had DLBCL histology and unfavorable parameters including stage IV, high IPI score and bone marrow BM involvement. Thus, the initial CNS involvement might be associated with advanced stage of lymphoma not with ovarian involvement itself. Surgical removal of involved ovary was performed in 20 patients (62%), and then they were treated with systemic chemotherapy. Twelve patients (38%) were treated with chemotherapy alone. The comparison of outcomes according to the treatment modalities showed the outcomes of chemotherapy-based treatment versus surgery-based treatment were not significantly different (2 year overall survival; 66% vs. 68%). With a median follow-up of 25 months (range 3-185), 13 patients (40.6%) relapsed. Two patients were relapsed in single lesion and 11 were relapsed in multiple lesions. The majority relapsed at various extranodal sites (11/13, 84.6%) and only 2 cases relapsed at nodal sites. Most common relapse site was CNS (4 cases among 13 cases of relapse, 31%). All CNS relapsed patients had DLBCL histology. Ovarian relapse observed in one case that had been involved both ovary at the time of diagnosis. The 2 year overall survivals (OS) were 67% (95% CI: 50 to 83%) and the 2 year progression free survivals (PFS) were 61% (95% CI: 44 to 78%). In univariate analysis, high IPI score, 2 or more extranodal sites involvement and elevated LDH level were statistically significant parameters for lower PFS; moreover, 2 or more extranodal sites involvement and elevated LDH level associated with poor OS. Conclusion Ovarian involvement of non-Hodgkin's lymphoma showed a dismal prognosis despite active treatment. Therefore, more optimal treatment strategy should be warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cauda Equina Syndrome as A Clinical Presentation of Extradural Diffuse B-Cell Non-Hodgkin’s Lymphoma: Case Report and Literature Review

2020 ◽  
Vol 3 (4) ◽  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Clinical Presentation ◽  
Cell Lymphoma ◽  
Cauda Equina ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Diffuse B Cell Lymphoma

Diffuse B-Cell Lymphoma corresponds to the most frequent pathological entity within the spectrum of Non-Hodgkin’s Lymphoma, with reported annual incidence of 24% in the U.S. literature.

Cost-Effectiveness of Rituximab for Maintenance in Patients with Follicular Non-Hodgkin’s Lymphoma in the Dutch Setting

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2364-2364
Author(s):  
Marjolein Pompen ◽  
P.C. Huijgens
Keyword(s):  
Economic Evaluation ◽  
Cost Effectiveness ◽  
Maintenance Therapy ◽  
Incremental Cost ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Rituximab Maintenance ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Cost

Abstract <>Cost-Effectiveness of Rituximab For Maintenance in Patients With Follicular Non-Hodgkin’s Lymphoma in the Dutch setting <>Rituximab (MabThera®/Rituxan®), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in the treatment of indolent and aggressive non Hodgkin’s lymphoma (NHL), including follicular lymphoma (FL). The purpose of the current economic evaluation was to estimate the cost-effectiveness of rituximab added in the maintenance setting for patients with relapsed/refractory FL. The cost-effectiveness of rituximab maintenance therapy in the Dutch healthcare system was assessed by economic modelling based on survival data from an EORTC/HOVON randomized clinical trial (EORTC20981/HOVON 39 NHL) in which patients with relapsed or refractory FL were randomized for maintenance rituximab vs no treatment after having responded to induction therapy. Utility values were obtained from a study in patients with FL using the EQ-5D York Tariff (unpublished). The primary endpoint was the incremental cost per quality adjusted life year (QALY) gained. A secondary endpoint was the incremental cost per life year gained (LYG). Only direct health care costs (drug acquisition, administration, adverse events, treatment at relapse, and routine surveillance) were included in the economic evaluation. Effects (QALYs and LYG) and costs accruing after the first year of the economic evaluation were discounted at the rate of 1.5% and 4% per annum, respectively. The economic evaluation was done by using a three state health state transition model. In this model, all patients start in the progression free (PFD) state with possible transitions to progressive disease (PD) or death (D). Progression free survival (PFS) and overall survival (OS) data were extrapolated over a period of 30 years with monthly cycles. Rituximab maintenance was more effective than observation in terms of both LYG and QALYs gained. The average discounted life expectancy in the rituximab group exceeded the observation group by 1.10 years (6.27 vs. 5.16); rituximab maintenance was associated with an additional 0.97 QALYs compared to observation. Total costs were €27,094 (euro 2006) higher in the rituximab group than the observation group and were largely due to the cost of the study drug and its administration. The incremental cost per QALY gained was €27,896 and the incremental cost per LYG was €24,564. The results from the EORTC20981/HOVON 39 NHL trial provide evidence of an incremental clinical benefit for rituximab maintenance therapy compared to ‘observation’ in patients with relapsed or refractory FL who have responded to CHOP or R-CHOP induction therapy. Subsequently, the results of the current economic modelling show that rituximab maintenance therapy has an incremental cost-effectiveness ratio of €27,896/QALY. The results were most sensitive to the duration of treatment benefit and the difference in treatment frequency and costs upon relapse between the two treatment groups. However, in all cases rituximab maintenance therapy remained a treatment that represents a cost-effective intervention. The economic analysis has shown to be adequately robust, hence it can be concluded that rituximab maintenance therapy in the Dutch setting is cost-effective.

Sign in / Sign up

Export Citation Format

Share Document