Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab
Bittenbring JT, Neumann F, Altmann B, Achenbach M, Reichrath J, Ziepert M, Geisel J, Regitz E, Held G, Pfreundschuh M
Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 94 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Deutsche Krebshilfe
Según 1 financiador declarado.
Publicación
- Publicado
- 2014-08-19 · J Clin Oncol · vol. 32 · número 29 · págs. 3242–3248
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 135 citas · más que el 99% de estudios similares · 9.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 22 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lymphoma Diagnosis and Treatment · Vitamin D Research Studies · CNS Lymphoma Diagnosis and Treatment
- Palabras clave
- vitamin D deficiency, diffuse large B-cell lymphoma, rituximab, R-CHOP, 25-hydroxyvitamin D3, vitamin D supplementation, elderly patients, event-free survival, overall survival, prognostic factors
- MeSH
- humans, vitamin d deficiency, cyclophosphamide, vincristine, doxorubicin, calcifediol, prednisone, antineoplastic agents, antineoplastic combined chemotherapy protocols, treatment outcome, risk factors, aged, aged, 80 and over, middle aged, female, male, lymphoma, large b-cell, diffuse, antibodies, monoclonal, murine-derived, rituximab
10 autores
- Joerg Thomas Bittenbring🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Frank Neumann🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Bettina Altmann🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Marina Achenbach🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Jörg Reichrath🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Marita Ziepert🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Jürgen Geisel🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Evi Regitz🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Gerhard Held🇩🇪Universitätsklinikum des Saarlandes; Leipzig University
- Michael G. Pfreundschuh🇩🇪 · autor de correspondenciaUniversitätsklinikum des Saarlandes; Leipzig University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Purpose
To investigate the impact and mechanisms of vitamin D deficiency (VDD) on the outcome of elderly patients with diffuse large B-cell lymphoma (DLBCL).
Patients and methods
Three hundred fifty-nine pretreatment 25-hydroxyvitamin D3 (25[OH]D3) serum levels from the RICOVER-60 study (Six Versus Eight Cycles of Biweekly CHOP-14 With or Without Rituximab in Elderly Patients With Aggressive CD20+ B-Cell Lymphomas) and 63 from the RICOVER-noRTh study (an amendment to the RICOVER-60 study in which patients received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone administered at an interval of 2 weeks plus two cycles of rituximab [R-CHOP-14], but without radiotherapy) were determined by chemoluminescent immunoassay. Rituximab-mediated cellular cytotoxicity (RMCC) was assessed by lactate dehydrogenase release assay of CD20+ Daudi cells.
Results
RICOVER-60 patients with VDD (≤ 8 ng/mL) and vitamin D levels more than 8 ng/mL treated with rituximab had 3-year event-free survival (EFS) of 59% and 79% and 3-year overall survival (OS) of 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for International Prognostic Index risk factors with a hazard ratio (HR) of 2.1 (P = .008) for EFS and 1.9 (P = .040) for OS. EFS was not significantly different in patients with vitamin D levels ≤ 8 or more than 8 ng/mL (HR, 1.2; P = .388) treated without rituximab. This was confirmed in an independent validation set of 63 RICOVER-noRTh patients. RMCC increased significantly (P < .001) in seven of seven individuals with VDD after substitution and normalization of their vitamin D levels.
Conclusion
VDD is a risk factor for elderly patients with DLBCL treated with R-CHOP. That VDD impairs RMCC and substitution improves RMCC strongly suggests that vitamin D substitution enhances rituximab efficacy, which must be confirmed in appropriately designed prospective trials addressing VDD and substitution not only in DLBCL, but also in malignancies treated with other antibodies, of which the major mechanism of action is antibody-dependent cellular cytotoxicity (eg, trastuzumab in breast cancer and cetuximab in colorectal cancer).
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