Cyclophosphamide, Bortezomib and Methylprednisolone (CyBorMe) for the Treatment of AL Amyloidosis: Initial Experience From a Single Center

Abstract

The use of cyclophosphamide, bortezomib and dexamethasone (CyBorD) is widely accepted in the treatment of AL amyloidosis (AL). Recently, the substitution of dexamethasone by methylprednisolone (CyBorMe) appeared to improve response rates and survival outcomes. All consecutive newly diagnosed AL amyloidosis treated with CyBorMe from 01/19 to 08/20 were evaluated. A historic cohort of patients treated with CyBorD was used for comparison (01/13–08/20). Methylprednisolone was given IV at 500 mg weekly for 4 weeks in the CyBorMe group. 43 patients were treated with CyBorD and 14 with CyBorMe. After a median of 4 cycles of CyBorD and 3 cycles of CyBorMe, Hematological Response was seen in 90.6% and 92.8% of cases, including CR in 28.5% and 35.7%, VGPR in 33.3% and 35.7% and PR in 30.9% and 21.4% for CyBorD and CyBorMe, respectively. Time to first response was faster in the CyBorMe group (4 vs. 6 weeks) and cardiac response was observed in 44% and 31% of patients treated with CyBorMe and CyBorD, respectively. CyBorMe appeared to be efficacious and well tolerated in patients with AL amyloidosis. Prospective studies with CyBorMe in the stage III/IV group are warranted aiming to minimize toxicity.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Vaxman I, Dispenzieri A, Muchtar E, Gertz M (2020) New developments in diagnosis, risk assessment and management in systemic amyloidosis. Blood Rev 40:100636

    CAS  Article  Google Scholar 

  2. 2.

    Richardson PG, Hideshima T, Anderson KC (2003) Bortezomib (PS-341): a novel, first-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancers. Cancer Control 10(5):361–369

    Article  Google Scholar 

  3. 3.

    Venner CP, Lane T, Foard D et al (2012) Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood 119(19):4387–4390

    CAS  Article  Google Scholar 

  4. 4.

    Mikhael JR, Schuster SR, Jimenez-Zepeda VH et al (2012) Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 119(19):4391–4394

    CAS  Article  Google Scholar 

  5. 5.

    Palladini G, Sachchithanantham S, Milani P et al (2015) A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood 126(5):612–615

    CAS  Article  Google Scholar 

  6. 6.

    Manwani R, Cohen O, Sharpley F et al (2019) A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib. Blood 134(25):2271–2280

    Article  Google Scholar 

  7. 7.

    Mahmood ASS, Harrison S, Manwani R, Sharpley F, Quarta C, Rezk T, Martinez A, Yoong K, Rabin N, Popat R, Kyriacou C, Papanikolau X, D'Sa S, Lachmann H, Whelan C, Gillmore J, Fontana M, Hawkins P, Wechaleckar A (2019) Bortezomib-High dose Methylprednisolone offers improved hematological response and overall survival compared to Bortezomib-Dexamethasone in Systemic Light Chain Amyloidosis. EHA Library. 2019:PB2127. Accessed 2019

  8. 8.

    Jimenez-Zepeda VH, Duggan P, Neri P, Bahlis NJ (2016) Bortezomib-containing regimens for the treatment of newly diagnosed and relapsed amyloid light chain amyloidosis: a single-center experience. Clin Lymphoma Myeloma Leuk 16(6):e79-84

    Article  Google Scholar 

  9. 9.

    Diaz-Pallares C, Lee H, Luider J et al (2020) Cyclophosphamide, bortezomib and dexamethasone (CyBorD) for the treatment of newly diagnosed AL amyloidosis: impact of response on survival outcomes. Clin Lymphoma Myeloma Leuk 20(6):394–399

    Article  Google Scholar 

  10. 10.

    Palladini G, Dispenzieri A, Gertz MA et al (2012) New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol 30(36):4541–4549

    CAS  Article  Google Scholar 

  11. 11.

    Gertz MA, Comenzo R, Falk RH, et al (2005) Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th international symposium on amyloid and amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol, 79(4):319-328

  12. 12.

    Merlini G, Seldin DC, Gertz MA (2011) Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol 29(14):1924–1933

    Article  Google Scholar 

  13. 13.

    Jiang F, Chen J, Liu H, Li L, Lu W, Fu R (2018) The effect and safety of bortezomib in the treatment of AL amyloidosis: a systematic review and meta-analysis. Indian J Hematol Blood Transfus 34(2):216–226

    Article  Google Scholar 

  14. 14.

    Tahir UA, Doros G, Kim JS, Connors LH, Seldin DC, Sam F (2019) Predictors of mortality in light chain cardiac amyloidosis with heart failure. Sci Rep 9(1):8552

    Article  Google Scholar 

  15. 15.

    Wechalekar AD, Schonland SO, Kastritis E et al (2013) A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 121(17):3420–3427

    CAS  Article  Google Scholar 

  16. 16.

    Manwani R, Foard D, Mahmood S et al (2018) Rapid hematologic responses improve outcomes in patients with very advanced (stage IIIb) cardiac immunoglobulin light chain amyloidosis. Haematologica 103(4):e165–e168

    CAS  Article  Google Scholar 

  17. 17.

    Zoorob RJ, Cender D (1998) A different look at corticosteroids. Am Fam Physician 58(2):443–450

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Victor H. Jimenez-Zepeda.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jimenez-Zepeda, V.H., Lee, H., Fine, N. et al. Cyclophosphamide, Bortezomib and Methylprednisolone (CyBorMe) for the Treatment of AL Amyloidosis: Initial Experience From a Single Center. Indian J Hematol Blood Transfus (2021). https://doi.org/10.1007/s12288-021-01406-z

Download citation

Keywords

  • CyBorMe
  • CyBorD
  • AL amyloidosis
  • Organ response