The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study
Abstract
Background Intravenous rituximab is a mainstay of treatment for follicular lymphoma. A subcutaneous formulation that achieves equivalent rituximab serum concentrations might improve convenience and save health-care resources without sacrificing clinical activity. We aimed to assess pharmacokinetic non-inferiority of 3 week cycles of fixed-dose subcutaneous rituximab versus standard intravenous rituximab.Methods In our two-stage, randomised, open-label, phase 3 trial, we enrolled patients with previously untreated grade 1-3a, CD20-positive follicular lymphoma at 67 centres in 23 countries. In stage 1, we randomly allocated patients 1:1 with the Pocock and Simon algorithm to intravenous rituximab (375 mg/m(2)) or fixed-dose subcutaneous rituximab (1400 mg), stratified by induction chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, prednisone or cyclophosphamide, vincristine, prednisone), Follicular Lymphoma International Prognostic Index score, and region. After randomisation, patients received one induction dose of intravenous rituximab in cycle 1 and then allocated treatment for cycles 2-8. Patients with a complete or partial response following induction therapy continued intravenous or subcutaneous rituximab as maintenance every 8 weeks. The primary endpoint was the ratio of observed rituximab serum trough concentrations (Ctrough) between groups at cycle 7 (before cycle 8 dosing) of induction treatment in a per-protocol population. Patients were analysed as treated for safety endpoints. Stage 2 follow-up is ongoing and is fully accrued. This study is registered with ClinicalTrials.gov, number NCT01200758.Findings Between Feb 4, 2010, and Oct 21, 2011, we enrolled 127 patients. Pharmacokinetic data were available for 48 (75%) of 64 patients randomly allocated intravenous rituximab and 54 (86%) of 63 patients randomly allocated subcutaneous rituximab. Geometric mean Ctrough was 83·13 μg/mL in the intravenous group and 134·58 μg/mL in the subcutaneous group (ratio 1·62, 90% CI 1·36-1·94), showing non-inferiority of subcutaneous rituximab. 57 (88%) of 65 patients in the intravenous rituximab safety population had adverse events (30 [46%] grade ≥3), as did 57 (92%) of 62 patients in the subcutaneous rituximab safety population (29 [47%] grade ≥3). The most common grade 3 or worse adverse event in both groups was neutropenia (14 [22%] patients in the intravenous group and 16 [26%] patients in the subcutaneous group). Adverse events related to administration were mostly grade 1-2 and occurred in 21 (32%) patients in the intravenous group and 31 (50%) patients in the subcutaneous group.Interpretation Stage 1 data show that the pharmacokinetic profile of subcutaneous rituximab was non-inferior to intravenous rituximab and was not associated with new safety concerns. Stage 2 will provide data for efficacy and safety of the subcutaneous administration.Funding F Hoffmann-La Roche.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Furthermore, population pharmacokinetic (PopPK) modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of mAbs could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment [20–23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
In the citing paper
“When developing the subcutaneous formulation for trastuzumab and rituximab, the change from intravenous to subcutaneous administration included a switch from weight- and body surface area-adjusted dosing to a fixed dose [21, 39, 74].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
In the citing paper
“The fixed-dose regimens for trastuzumab and rituximab were further supported by exposure–response analyses of response and grade ≥ 3 adverse events, which did not identify a statistically meaningful impact of bodyweight or body surface area, respectively, nor of exposure or route of administration of the respective mAbs [21, 74].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
In the citing paper
“In both the HannaH and the Sabrina studies, subcutaneous administration of trastuzumab and rituximab resulted in noninferior Ctrough and efficacy to intravenous dosing and a similar safety profile [21, 39, 74].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
In the citing paper
“Overall response at the end of induction was 84.9% (95% CI 79.2–89.5) in the intravenous group and 84.4% (78.7–89.1) in the subcutaneous group.”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
In the citing paper
“In Sabrina, the geometric mean ratio of Ctrough subcutaneous to Ctrough intravenous was 1.5 (90% CI 1.3–1.7).”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
In the citing paper
“With the pivotal noninferiority trials for trastuzumab and rituximab, the HannaH and Sabrina studies, respectively, two larger head-to-head studies comparing the immunogenicity of intravenous versus subcutaneous administration with the same dosing regimen have become available [21, 74].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [21]
Citations
Cites
Cheson, B. D., Horning, S., Coiffier, B., Shipp, M., Fisher, R. I., Connors, J. M., Lister, T., Vose, J., Grillo-López, A., Hagenbeek, A., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.4.1244 · Cited by 3,210
Pocock, S. J., & Simon, R. (1975) · Biometrics · doi:10.2307/2529712 · Cited by 2,350
Hiddemann, W. (2005) · Blood · doi:10.1182/blood-2005-01-0016 · Cited by 1,317
Salles, G., Seymour, J. F., Offner, F. C., López‐Guillermo, A., Belada, D., Xerri, L., Feugier, P., Bouabdallah, R., Catalano, J. V., Brice, P., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)62175-7 · Cited by 1,075
Marcus, R. E., Imrie, K., Solal‐Céligny, P., Catalano, J. V., Dmoszyńska, A., Raposo, J. C., Offner, F. C., Gómez‐Codina, J., Belch, A. R., Cunningham, D., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.5376 · Cited by 591
Self-citationRituximab Dose-Escalation Trial in Chronic Lymphocytic Leukemia
O'Brien, S. M., Kantarjian, H. M., Thomas, D. A., Giles, F. J., Freireich, E. J., Cortes, J. E., Lerner, S. A., & Keating, M. J. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.8.2165 · Cited by 585
Lundin, J., Kimby, E., Björkholm, M., Broliden, P.-A., Celsing, F., Hjalmar, V., Möllgård, L., Rebello, P., Hale, G., Waldmann, H., et al. (2002) · Blood · doi:10.1182/blood-2002-01-0159 · Cited by 497
Ismael, G., Hegg, R., Muehlbauer, S., Heinzmann, D., Lum, B., Kim, S.-B., Pienkowski, T., Lichinitser, M., Semiglazov, V., Melichar, B., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70329-7 · Cited by 351
van Oers, M. H. J., Glabbeke, M. M. V., Giurgea, L., Klasa, R. J., Marcus, R. E., Wolf, M. M., Kimby, E. K., Veer, M. B. V., Vranovský, A., Holte, H., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.5827 · Cited by 327
Frost, G. I. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.4.4.427 · Cited by 323
Höchster, H. S., Weller, E. A., Gascoyne, R. D., Habermann, T. M., Gordon, L. I., Ryan, T. M., Zhang, L., Colocci, N., Frankel, S., & Horning, S. J. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.1561 · Cited by 276
Stilgenbauer, S., Zenz, T., Winkler, D. F. H., Bühler, A., Schlenk, R. F., Groner, S., Busch, R. M., Hensel, M., Dührsen, U., Finke, J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.1128 · Cited by 269
Pivot, X., Gligorov, J., Müller, V., Barrett-Lee, P., Verma, S., Knoop, A., Curigliano, G., Semiglazov, V., López-Vivanco, G., Jenkins, V., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70383-8 · Cited by 230
Fixed Dosing Versus Body Size—Based Dosing of Monoclonal Antibodies in Adult Clinical Trials
Wang, D. D., Zhang, S., Zhao, H., Men, A. Y., & Parivar, K. (2009) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009337512 · Cited by 192
Mathijssen, R. H. J., de Jong, F. A., Loos, W. J., van der Bol, J. M., Verweij, J., & Sparreboom, A. (2007) · The Oncologist · doi:10.1634/theoncologist.12-8-913 · Cited by 146
Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase
Shpilberg, O., & Jackisch, C. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.371 · Cited by 138
Wynne, C., Harvey, V. J., Schwabe, C., Waaka, D., McIntyre, C., & Bittner, B. (2012) · The Journal of Clinical Pharmacology · doi:10.1177/0091270012436560 · Cited by 127
Self-citationTobinai, K., Igarashi, T., Itoh, K., Kobayashi, Y., Taniwaki, M., Ogura, M., Kinoshita, T., Hotta, T., Aikawa, K., Tsushita, K., et al. (2004) · Annals of Oncology · doi:10.1093/annonc/mdh176 · Cited by 108
Bittner, B., Richter, W., Hourcade‐Potelleret, F., McIntyre, C., Herting, F., Zepeda, M. L., & Schmidt, J. (2012) · Arzneimittelforschung · doi:10.1055/s-0032-1321831 · Cited by 57
Self-citationGoldenberg, D. M., Morschhauser, F., & Wegener, W. A. (2010) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428191003672123 · Cited by 56
High-dose rituximab therapy in chronic lymphocytic leukemia.
Keating, M., & O'Brien, S. (2000) · PubMed · Cited by 42
Horseshoes, Hand Grenades, and Body-Surface Area–Based Dosing: Aiming for a Target
Egorin, M. J. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.10.084 · Cited by 40
Bittner, B., Richter, W., Hourcade‐Potelleret, F., McIntyre, C., Herting, F., Zepeda, M. L., & Schmidt, J. (2013) · Drug Research · doi:10.1055/s-0033-1357211 · Cited by 38
Self-citationYin, A., Li, J., Hurst, D. W., & Visich, J. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.e13108 · Cited by 16
Salar, A., Bouabdallah, R., McIntyre, C., Sayyed, P. Z., & Bittner, B. (2010) · Blood · doi:10.1182/blood.v116.21.2858.2858 · Cited by 12
Self-citationSalar, A., Avivi, I. M., Larouche, J.-F., Janíková, A., Pereira, J. C., Brewster, M., Catalani, O., McIntyre, C., Sayyed, P. Z., & Haynes, A. (2012) · Blood · doi:10.1182/blood.v120.21.1641.1641 · Cited by 8
Self-citationDe Cock, E., Kritikou, P., Tao, S., Wiesner, C., Waterboer, T., & Carella, A. M. (2013) · Blood · doi:10.1182/blood.v122.21.1724.1724 · Cited by 7
Cited by
Sorted by citations
Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience
Salles, G., Barrett, M., Foà, R., Maurer, J., O'Brien, S. M., Valente, N., Wenger, M., & Maloney, D. G. (2017) · Advances in Therapy · doi:10.1007/s12325-017-0612-x · Cited by 620
Self-citationSubcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities
Bittner, B., Richter, W., & Schmidt, J. (2018) · BioDrugs · doi:10.1007/s40259-018-0295-0 · Cited by 447
Self-citationPast, Present, and Future of Rituximab—The World’s First Oncology Monoclonal Antibody Therapy
Pierpont, T. M., Limper, C., & Richards, K. L. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00163 · Cited by 402
Roccatello, D., Saadoun, D., Ramos‐Casals, M., Tzioufas, A. G., Fervenza, F. C., Cacoub, P., Zignego, A. L., & Ferri, C. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0009-4 · Cited by 223
Tan, A. R., Im, S., Mattar, A. P. L., Colomer, R., Stroyakovskiy, D., Nowecki, Z. I., Laurentiis, M. D., Pierga, J., Jung, K. H., Schem, C., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30536-2 · Cited by 186
Metadata
- Authors
- Davies, A., Merli, F., Mihaljevic, B., Siritanaratkul, N., Solal-Céligny, P., Barrett, M., Berge, C., Bittner, B., Boehnke, A., McIntyre, C., & MacDonald, D.
- Affiliations
- Cancer Research UK (GB)
- Santa Maria Nuova Hospital (IT)
- Siriraj Hospital (TH)
- Institut de Cancérologie de l'Ouest (FR)
- Roche (United Kingdom) (GB)
- F. Hoffmann-La Roche AG (CH)
- Queen Elizabeth II Health Sciences Centre (CA)
- Corresponding author
- Davies, Andrew
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 15
- Issue
- 3
- Pages
- 343-352
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2120711586
- Cited by
- 114
- References
- 27
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 7 · 2019: 7 · 2018: 13 · 2017: 13 · 2016: 16 · 2015: 12 · 2014: 6
- FWCI
- 11.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- F. Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- follicular lymphoma, pharmacokinetics, non-inferiority, CD20-positive lymphoma, maintenance therapy, induction chemotherapy, fixed-dose dosing, adverse events, drug safety, previously untreated lymphoma, R-CHOP
- MeSH terms
- Rituximab, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Female, Humans, Injections, Subcutaneous, Lymphoma, Follicular, Male, Middle Aged, Neoplasm Staging, Antibodies, Monoclonal, Murine-Derived
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
