formulation for subcutaneous administration

Rituximab (MabThera) for subcutaneous administration, new opportunities well-studied drug

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES ,

G.S. Tumyan

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation

ABSTRACT

The current concept of anticancer therapy optimization means reduction of health care costs, decreased toxicity with the same or greater efficacy of the administered drug, and, as the result, more comfortable and convenient management of cancer patients. The new formulation of Rituximab (Mabthera) for subcutaneous (SC) administration meets all above criteria. The clinical studies of this drug demonstrate non-inferiority of the fixed dose 1400 mg SC compared to the approved dose of 375 mg/m2 intravenously. Mabthera SC shows the safety profile similar to the formulation for intravenous administration and makes the delivery of the drug faster (mean SC injection time = 10 minutes), safer, and more convenient for patients.

Keywords: Mabthera, formulation for subcutaneous administration.

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REFERENCES

  1. Stilgenbauer S., Zenz T., Winkler D. et al. Subcutaneous Alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J. Clin. Oncol. 2009; 27: 3994–4001.
  2. Frost G. Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert. Opin. Drug Deliv. 2007; 4(4): 427–40.
  3. Salar A., Bouabdallah R., McIntyre C. et al. A Two-stage phase Ib study to investigate the pharmacokinetics, safety and tolerability of subcutaneous Rituximab in patients with follicular lymphoma as part of maintenance treatment. Blood 2010; 116: Abstract 2858.
  4. Bai S., Jorga K. et al. A guide to rational dosing of monoclonal antibodies. J. Clin. Pharmac. 2012; 51(2): 119–35.
  5. Wang D.D., Zhang S., Zhao H., Men A.Y., Parivar K. Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials. J. Clin. Pharmacol. 2009; 49(9): 1012–24.
  6. Assouline S., Buccheri V., Delmer A. et al. Subcutaneous Rituximab in combination with fludarabine and cyclophosphamide for patients with CLL: initial results of a phase Ib study (SAWYER [BO25341]) show non-inferior pharmacokinetics and comparable safety to that of intravenous Rituximab. ASH Annual Meeting Abstracts 2012: Abstract 1637.
  7. Davies A., Merli F., Mihaljevik B. et al. Pharmacokinetics, safety and overall response rate achieved with subcutaneous administration of Rituximab in combination with chemotherapy were comparable to those achieved with intravenous administration in patients with follicular lymphoma in the first-line setting: stage 1 results of the phase III SABRINA Study (BO22334). ASH Annual Meeting Abstracts 2012: Abstract 1629.
  8. Davies A., Merli F., Mihaljevik B. et al. Pharmacokinetics and safety of subcutaneous Rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study.// Lancet Oncol. Published Online February 10, 2014.
  9. Стойкое восстановление донорского гемопоэза у больной с посттрансплантационным рецидивом острого миеломонобластного лейкоза с inv(3)(q21q26), –7 и экспрессией онкогена EVI1 после трансфузий донорских лимфоцитов и использования гипометилирующих агентов
  10. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Лейкозы и миелодис- пластические синдромы с высокой экспрессией гена EVI1: теоретические и клинические аспекты. Клин. онкогематол. 2012; 5(4): 361–4. [Mamayev N.N., Gorbunova A.V., Gindina T.L. et al. Leukemias and myelodisplastic syndromes with high EVI1 gene expression: theoretical and clinical aspects. Klin. onkogematol. 2012; 5(4): 361–4. (In Russ.)].
  11. Barrett A.J., Battiwalla M. Relapse after allogeneic stem cell transplantation. Expert. Rev. Hematol. 2010; 3(4): 429–41.
  12. Arellano M.L., Langston A., Winton E. et al. Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience. Biol. Blood Marrow Transplant. 2007; 13(1): 116–23.
  13. Porter D.L., Alyea E.P., Antin J.H. et al. NCI First International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol. Blood Marrow Transplant. 2010; 16: 1467–503.
  14. Pavletic S.Z., Kumar S., Mohty M. et al. NCI First International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: Report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol. Blood Marrow Transplant. 2010; 16: 871–90.
  15. Wang Y., Liu D.-H., Fan Z.-P. et al. Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study. Clin. Transplant. 2012. doi: 10.111/j.1399-0012.2012.01626.x.
  16. Lubbert M., Bertz H., Wasch R. et al. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant. 2009; 45(4): 627–32.
  17. Craddock C., Quek L., Goardon N. et al. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia 2012; doi: 10.1038/leu.2012.312.
  18. Candoni A., Tiribelli M., Toffoletti E. et al. Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia. Eur. J. Haematol. 2009; 82(1): 61–8.
  19. Zhao X.-S., Jin S., Zhu H.-H. et al. Wilms’ tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011. doi:10.1038/bmt.2011.121.