Role of antibody-based therapy in indolent non-Hodgkin's lymphoma
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ABSTRACT:
SUBMITTER: Willard P
PROVIDER: S-EPMC8569585 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:For patients with advanced indolent non-Hodgkin's lymphoma (NHL) or elderly patients with mantle cell lymphoma (MCL), the recently reported results of the German StiL NHL-1 2003 and the international BRIGHT phase III trials showed that, as first-line treatment, the combination of bendamustine and rituximab is at least as effective as rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone or rituximab/cyclophosphamide/vincristine/prednisone, possibly with a better therapeutic index. Bendamustine is therefore increasingly used in clinical practice. Because bendamustine has been used for many years in Germany and in Switzerland, our institutions have had extensive experience with bendamustine, both as a single agent and in combination with rituximab. In this comprehensive review, we summarize the most important clinical data from phase II/III trials with bendamustine in patients with indolent NHL and MCL, both in the relapsed/refractory setting and in the first-line setting. In addition, this review provides practical advice on how to optimally manage bendamustine therapy in patients with NHL.
| S-EPMC3755934 | biostudies-other
Project description:Mantle cell lymphoma (MCL) comprises 3-10% of NHL, with survival times ranging from 3 and 5 years. Indolent lymphomas represent approximately 30% of all NHLs with patient survival largely dependent on validated prognostic scores. High response rates are typically achieved in these patients with current first-line chemoimmunotherapy. However, most patients will eventually relapse and become chemorefractory with poor outcome. Alternative chemoimmunotherapy regimens are often used as salvage strategy and stem cell transplant remains an option for selected patients. However, novel approaches are urgently needed for patients no longer responding to conventional chemotherapy. Lenalidomide is an immunomodulatory drug with activity in multiple myeloma, myelodisplastic syndrome and chronic lymphoproliferative disorders. In phase II studies of indolent NHL and MCL lenalidomide has shown activity with encouraging response rates, both as a single agent and in combination with other drugs. Some of these responses may be durable. Optimal dose of lenalidomide has not been defined yet. The role of lenalidomide in the therapeutic armamentarium of patients with indolent NHL or MCL will be discussed in the present paper.
| S-EPMC3384930 | biostudies-literature
Project description:Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies.A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers.Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 ?g/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative.Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).
| S-EPMC3069234 | biostudies-literature
Project description:To analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin's lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan-Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87 months (95% CI 72-102 months). Median single dose per fraction was 2.0 Gy (range 1.5-2 Gy) and median total dose was 30.6 Gy (range 16-45 Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0 years (95% CI 8.3-19.7 years). The estimated PFS after 5 and 10 years were 73.0% and 65.5% in Kaplan-Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60 years old) had significantly superior PFS to those older than 60 years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0 Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I-II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I-II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6 months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I-II side effects recovered 3 to 6 months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy.Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19-137).
| S-EPMC8604980 | biostudies-literature
Project description:PurposeWe performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma.Patients and methodsIn this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability.ResultsAll 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue.ConclusionOral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.
| S-EPMC3083875 | biostudies-literature
Project description:PURPOSE: The aim was to investigate the potential impact of positron emission tomography (PET)/computed tomography (CT) as compared to PET and CT on the staging of patients with indolent lymphoma. PROCEDURES: PET/CTs from 45 patients with indolent lymphoma undergoing staging or restaging were studied. Clinical follow-up, additional imaging, and histology served as the gold standard. RESULTS: PET/CT correctly diagnosed 92 nodal regions as positive for lymphomatous involvement and 458 as disease free vs 68 and 449 for PET and 64 and 459 for CT, respectively. The respective sensitivities, specificities, and accuracies were 99%, 100%, and 99.8% for PET/CT, 68%, 97.5%, and 92.2% for PET, and 70%, 100%, and 94.7% for CT. PET/CT performed significantly better than PET (p < 0.001 for sensitivity, specificity, and accuracy) and CT (p < 0.001 for sensitivity and accuracy). PET/CT also correctly identified significantly more extra-nodal lesions (22) than CT (14) and PET (nine). CONCLUSIONS: PET/CT provides significantly more accurate information compared to PET and CT for the staging and re-staging of patients with indolent lymphoma.
| S-EPMC2693779 | biostudies-other
Project description:We report corresponding gene expression, promoter methylation patterns of differential DHSs as well as differentially occupied TF binding motifs using surrounding DNAseI cut profiles. Overall, our study provides a framework for model studies of HL and NHL pathologies.
2014-09-24 | GSE51813 | GEO
Project description:Cell adhesion is of fundamental importance in the cell communication, signaling and motility, and its dysfunction occurs prevalently during cancer progression. The knowledge of the molecular and cellular processes involved in abnormalities in cancer cells adhesion has dramatically increased and it has been focused mainly on cellular adhesion molecules (CAMs) and tumor microenvironment. During the last decade, several methods for measuring and studying cell adhesion properties were also developed, including optical tweezers technology. We have developed a non-invasive method employing optical tweezers technology in order to differentiate normal B-cells and non-Hodgkin’s lymphoma cells derived from clinical samples. Our approach bases on nascent adhesion formation between B-cell and mesenchymal stromal cell. In this method, a single B-cell is trapped and optically seeded on mesenchymal stromal cell and maintained direct contact until stable connection between cells is formed in time-scale. After we characterized the adhesive properties of the panel of clinical samples, we performed the deep proteomics investigations on cellular adhesion proteins using liquid chromatography- tandem mass spectrometry (LC-MS/MS).
2021-09-08 | PXD011683 | Pride
Project description:We report corresponding gene expression, promoter methylation patterns of differential DHSs as well as differentially occupied TF binding motifs using surrounding DNAseI cut profiles. Overall, our study provides a framework for model studies of HL and NHL pathologies. Examination of DNA Methylation in L1236, L428, Reh and Namalwa cell lines.
2014-09-24 | E-GEOD-51813 | biostudies-arrayexpress
Project description:Immune-based therapies mobilize the immune system to promote or restore an effective antitumor immune response [...].
| S-EPMC8305599 | biostudies-literature