Humanized anti–interleukin-6 receptor antibody treatment of multicentric Castleman disease
Open accessAbstract
Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti–human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A humanized monoclonal antibody against IL-6 receptor, tocilizumab, has proven successful for treating rheumatoid arthritis and Castleman's disease.
“Instead of murine MoAb against IL-6, a humanized MoAb against IL-6 receptor (IL-6R), tocilizumab, has proven successful for treating RA and Castleman’s disease (71–75).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [72]
The Study drug section identifies MRA as a humanized anti–IL-6 receptor antibody, and the Discussion reports that it alleviated symptoms in patients with multicentric Castleman disease. The paper does not report successful treatment of rheumatoid arthritis. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe anti-IL-6R antibodies tocilizumab and sarilumab are used to treat RA, Castleman's disease and CAR-T-induced CRS.
“The anti-IL-6R antibodies tocilizumab and sarilumab are used to treat RA, Castleman’s disease and CAR-T-induced CRS (71–75, 352, 364) and have promise for treating the severe form of COVID-19 (365–367).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [72]
The Study drug and Discussion sections describe MRA as an anti-IL-6R antibody used to treat multicentric Castleman disease, and the study reports improvement in those patients. Our copy does not identify MRA as tocilizumab or address sarilumab, rheumatoid arthritis treatment, or CAR-T-induced CRS, so it supports only the Castleman disease portion of the attributed claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBoth siltuximab and tocilizumab have been shown to resolve disease flares and sustain remission in approximately one third to one half of patients with idiopathic multicentric Castleman's disease.
“Both siltuximab and tocilizumab have been shown to resolve disease flares and sustain remission in approximately one third to one half of patients.80”
From Cytokine storm (2020) · cites this paper as [80]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease.
Soulier, J., Grollet, L., Oksenhendler, E., Cacoub, P., Cazals-Hatem, D., Babinet, P., d'Agay, M., Clauvel, J., Raphael, M., Degos, L., et al. (1995) · Blood · doi:10.1182/blood.v86.4.1276.bloodjournal8641276 · Cited by 2,296 · see citing works
Kishimoto, T. (1989) · Blood · doi:10.1182/blood.v74.1.1.bloodjournal7411 · Cited by 2,068 · see citing works
Self-citationPathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease
Yoshizaki, K., Matsuda, T., Nishimoto, N., Kuritani, T., Taeho, L., Aozasa, K., Nakahata, T., Kawai, H., Tagoh, H., & Komori, T. (1989) · Blood · doi:10.1182/blood.v74.4.1360.1360 · Cited by 928 · see citing works
Self-citationGillmore, J. D., Lovat, L. B., Persey, M. R., Pepys, M. B., & Hawkins, P. N. (2001) · The Lancet · doi:10.1016/s0140-6736(00)05252-1 · Cited by 586 · see citing works
Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy
Nishimoto, N., Sasai, M., Shima, Y., Nakagawa, M., Matsumoto, T., Shirai, T., Kishimoto, T., & Yoshizaki, K. (2000) · Blood · doi:10.1182/blood.v95.1.56.001k13_56_61 · Cited by 445 · see citing works
Self-citationFrizzera, G., Peterson, B. A., Bayrd, E. D., & Goldman, A. I. (1985) · Journal of Clinical Oncology · doi:10.1200/jco.1985.3.9.1202 · Cited by 380 · see citing works
Beck, J. T., Hsu, S.-M., Wijdenes, J., Bataille, R., Klein, B., Vesole, D. H., Hayden, K., Jagannath, S., & Barlogie, B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199403033300904 · Cited by 322 · see citing works
Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth.
Sato, K., Tsuchiya, M., Saldanha, J. W., Koishihara, Y., Ohsugi, Y., Kishimoto, T., & Bendig, M. M. (1993) · PubMed · Cited by 274 · see citing works
Self-citationPaleolog, E. M., Hunt, M., Elliott, M. J., Feldmann, M., Maini, R. N., & Woody, J. N. (1996) · Arthritis & Rheumatism · doi:10.1002/art.1780390703 · Cited by 240 · see citing works
Multicentric Castleman's disease
Wang, Q. (2000) · Cited by 235 · see citing works
Antoine Gessain, A., Sudaka, A., Brière, J., et al. (1996) · Blood · doi:10.1182/blood.v87.1.414.bloodjournal871414 · Cited by 157 · see citing works
Tobinai, K., Kobayashi, Y., Narabayashi, M., Ogura, M., Kagami, Y., MORISHIMA, Y., Ohtsu, T., Igarashi, T., Sasaki, Y., Kinoshita, T., et al. (1998) · Annals of Oncology · doi:10.1023/a:1008265313133 · Cited by 150 · see citing works
Corbellino, M., Bestetti, G., Scalamogna, C., et al. (2001) · Blood · doi:10.1182/blood.v98.12.3473 · Cited by 141 · see citing works
Herpes-Like DNA Sequences, AIDS-Related Tumors, and Castleman's Disease
Karcher, D. S., & Alkan, S. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509213331211 · Cited by 139 · see citing works
LEVAN, A. (1956) · Cancer · doi:10.1002/1097-0142(195607/08)9:4 · Cited by 110 · see citing works
Herpes-like DNA sequences, AIDS-related tumors, and Castleman's disease.
Dupin, N., Gorin, I., Deleuze, J., et al. (1995) · PubMed · Cited by 79 · see citing works
Application of neural networks in structure-activity relationships
K�vesdi, I., Dominguez‐Rodriguez, M. F., �rfi, L., N�ray-Szab�, G., Varró, A., Papp, J. G., & M�tyus, P. (1999) · Medicinal Research Reviews · doi:10.1002/(sici)1098-1128(199905)19:3 · Cited by 62 · see citing works
Nishimoto, N., Ito, A., Ono, M., Tagoh, H., Matsumoto, T., Tomita, T., Ochi, T., & Yoshizaki, K. (2000) · International Immunology · doi:10.1093/intimm/12.2.187 · Cited by 52 · see citing works
Self-citationSimko, R., Nagy, K. L., Lombay, B., et al. (2000) · The American journal of pediatric hematology/oncology · doi:10.1097/00043426-200003000-00021 · Cited by 21 · see citing works
A patient on hydroxyurea for sickle cell disease who developed an opportunistic infection
Venigalla, P., Motwani, B., Nallari, A., et al. (2002) · Blood · doi:10.1182/blood-2002-03-0754 · Cited by 18 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Castleman B, Iverson L, Menendez VP. Localized mediastinal lymph-node hyperplasia resembling thymoma. Cancer. 1956;9:822-830.
- Flendrig JA, Schillings PHM. Benign giant lym- phoma: the clinical signs and symptoms. Folia Med Neerl. 1969;12:119-120.
- Keller AR, Hochholzer L, Castleman B. Hyaline- vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer. 1972;29:670-683.
- Peterson BA, Frizzera G. Multicentric Castle- man's disease. Semin Oncol. 1993;20:636-647.
- Argiles JM, Lopez-Soriano FJ. The role of cyto- kines in cancer cachexia. Med Res Rev. 1999;20: 223-248.
Cited by
Sorted by citations
Fajgenbaum, D. C., & June, C. H. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2026131 · Cited by 3,196 · see citing works
Current concepts in the diagnosis and management of cytokine release syndrome.
Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., Grupp, S. A., & Mackall, C. L. (2014) · Blood · doi:10.1182/blood-2014-05-552729 · Cited by 2,806 · see citing works
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
Jones, S. A., & Jenkins, B. J. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0066-7 · Cited by 1,102 · see citing works
Rose-John, S. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4989 · Cited by 1,040 · see citing works
IL-6 pathway in the liver: From physiopathology to therapy
Schmidt-Arras, D., & Rose-John, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.004 · Cited by 881 · see citing works
Targeting Interleukin-6 Signaling in Clinic
Kang, S., Tanaka, T., Narazaki, M., & Kishimoto, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.026 · Cited by 870 · see citing works
Self-citationThe wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
Naugler, W. E., & Karin, M. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.007 · Cited by 730 · see citing works
Pedersen, B. K. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048074 · Cited by 668 · see citing works
Cytokines and their relationship to the symptoms and outcome of cancer
Seruga, B., Zhang, H., Bernstein, L. J., & Tannock, I. F. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2507 · Cited by 652 · see citing works
Dispenzieri, A., & Fajgenbaum, D. C. (2020) · Blood · doi:10.1182/blood.2019000931 · Cited by 487 · see citing works
van Rhee, F., Wong, R. S., Munshi, N., Rossi, J.-F., Ke, X.-Y., Fosså, A., Simpson, D., Capra, M., Liu, T., Hsieh, R. K., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70319-5 · Cited by 454 · see citing works
The role of IL-6 in host defence against infections: immunobiology and clinical implications
Rose-John, S., Winthrop, K., & Calabrese, L. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.83 · Cited by 424 · see citing works
Iron Sequestration and Anemia of Inflammation
Ganz, T., & Nemeth, E. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.06.001 · Cited by 361 · see citing works
Dijkgraaf, E. M., Heusinkveld, M., Tummers, B., Vogelpoel, L. T. C., Goedemans, R., Jha, V., Nortier, J. W. R., Welters, M. J. P., Kroep, J. R., & van der Burg, S. H. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3542 · Cited by 346 · see citing works
Kraakman, M. J., Kammoun, H. L., Allen, T. L., Deswaerte, V., Henstridge, D. C., Estevez, E., Matthews, V. B., Neill, B., White, D. A., Murphy, A. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.006 · Cited by 257 · see citing works
Hepcidin in Human Iron Disorders: Diagnostic Implications
Kroot, J. J., Tjalsma, H., Fleming, R. E., & Swinkels, D. W. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2009.140053 · Cited by 246 · see citing works
Song, S.-N. J., Tomosugi, N., Kawabata, H., Ishikawa, T., Nishikawa, T., & Yoshizaki, K. (2010) · Blood · doi:10.1182/blood-2010-03-271791 · Cited by 228 · see citing works
Self-citationPolizzotto, M. N., Uldrick, T. S., Wang, V., Aleman, K., Wyvill, K. M., Marshall, V., Pittaluga, S., O’Mahony, D., Whitby, D., Tosato, G., et al. (2013) · Blood · doi:10.1182/blood-2013-08-519959 · Cited by 158 · see citing works
Fajgenbaum, D. C., Langan, R.-A., Japp, A. S., Partridge, H. L., Pierson, S. K., Singh, A., Arenas, D. J., Ruth, J. R., Nabel, C. S., Stone, K., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126091 · Cited by 147 · see citing works
IL-6 Revisited: From Rheumatoid Arthritis to CAR T Cell Therapy and COVID-19
Kishimoto, T., & Kang, S. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101220-023458 · Cited by 140 · see citing works
Self-citationHarden, L. M., Plessis, I. D., Poole, S., & Laburn, H. P. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.12.006 · Cited by 118 · see citing works
Kumar, V., & Choudhry, V. P. (2010) · The Indian Journal of Pediatrics · doi:10.1007/s12098-010-0120-3 · Cited by 100 · see citing works
Casper, C., Chaturvedi, S., Munshi, N., Wong, R., Qi, M., Schaffer, M., Bandekar, R., Hall, B., van de Velde, H., Vermeulen, J., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0134 · Cited by 97 · see citing works
Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease
Pierson, S. K., Stonestrom, A. J., Shilling, D., Ruth, J., Nabel, C. S., Singh, A., Ren, Y., Stone, K., Li, H., van Rhee, F., et al. (2018) · American Journal of Hematology · doi:10.1002/ajh.25123 · Cited by 90 · see citing works
The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases
Wang, M.-J., Zhang, H.-L., Chen, F., Guo, X.-J., Liu, Q.-G., & Hou, J. (2024) · Experimental Hematology & Oncology · doi:10.1186/s40164-024-00527-1 · Cited by 84 · see citing works
Increased mTOR activation in idiopathic multicentric Castleman disease
Arenas, D. J., Floess, K., Kobrin, D., Pai, R.-A. L., Srkalovic, M. B., Tamakloe, M.-A., Rasheed, R., Ziglar, J., Khor, J., Parente, S. A. T., et al. (2020) · Blood · doi:10.1182/blood.2019002792 · Cited by 83 · see citing works
Pai, R.-A. L., Japp, A. S., Gonzalez, M., Rasheed, R. F., Okumura, M., Arenas, D., Pierson, S. K., Powers, V., Layman, A. A. K., Kao, C., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.135031 · Cited by 68 · see citing works
Løbner, M., Walsted, A., Larsen, R., Bendtzen, K., & Nielsen, C. H. (2008) · Journal of Medicinal Food · doi:10.1089/jmf.2007.564 · Cited by 66 · see citing works
Ramaswami, R., Lurain, K., Peer, C. J., Serquiña, A., Wang, V., Widell, A., Goncalves, P., Steinberg, S. M., Marshall, V., George, J., et al. (2020) · Blood · doi:10.1182/blood.2019004602 · Cited by 51 · see citing works
- Authors
- Nishimoto, N., Kanakura, Y., Aozasa, K., Johkoh, T., Nakamura, M., Nakano, S., Nakano, N., Ikeda, Y., Sasaki, T., Nishioka, K., Hara, M., Taguchi, H., Kimura, Y., Kato, Y., Asaoku, H., Kumagai, S., Kodama, F., Nakahara, H., Hagihara, K., Yoshizaki, K., & Kishimoto, T.
- Affiliations
- Tokyo Medical and Dental University (JP)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-10-15
- Volume
- 106
- Issue
- 8
- Pages
- 2627-2632
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2171799063
- Cited by
- 754
- References
- 21
- Citations by year
- 2026: 17 · 2025: 24 · 2024: 37 · 2023: 33 · 2022: 30 · 2021: 29 · 2020: 46 · 2019: 24 · 2018: 29 · 2017: 46 · 2016: 39 · 2015: 45 · 2014: 47 · 2013: 47 · 2012: 47
- FWCI
- 15.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chugai Pharmaceutical
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- multicentric Castleman disease, IL-6 receptor, anti-IL-6 receptor monoclonal antibody, humanized monoclonal antibody, lymphoproliferative disorders, lymphadenopathy, chronic inflammation, fatigue, corticosteroid tapering, treatment efficacy and safety
- MeSH terms
- Adult, Aged, Antibodies, Body Weight, Female, Follow-Up Studies, Castleman Disease, Humans, Male, Middle Aged, Treatment Outcome, Receptors, Interleukin-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
