Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Safety and efficacy of propylene glycol-free melphalan as conditioning in patients with AL amyloidosis undergoing stem cell transplantation

Bone Marrow Transplantation volume 54, pages 1077–1081 (2019)Cite this article

Subjects

Abstract

High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations require propylene glycol (PG) as a co-solvent and melphalan has limited solubility and chemical stability after reconstitution, with potential risks for propylene glycol-related complications. Captisol-stabilized propylene glycol-free (PG-free) melphalan has been developed with improved solubility and chemical stability. We compared a cohort of patients with AL amyloidosis receiving PG melphalan (n = 96) to those receiving PG-free melphalan (n = 48) as conditioning for autologous stem cell transplantation. Median time to neutrophil and platelet engraftment was the same; 14 days PG melphalan vs 14 days PG-free melphalan, p = 0.73 and 16 days PG melphalan vs 16 days PG-free melphalan, p = 0.52, respectively. Hospitalization rate was similar in both cohorts, 68% PG melphalan vs 58% PG-free melphalan, p = 0.27. All-cause mortality at 100 days was not statistically significant, 3% PG melphalan vs 2% PG-free melphalan, p > 0.99. Overall response rate (ORR) and rates of complete response (CR) were similar (ORR 93% PG melphalan vs 94% PG-free melphalan, p > 0.99 and CR 39% PG melphalan vs 32% PG-free melphalan, p = 0.46). PG-free melphalan showed a comparable safety and efficacy profile to PG melphalan in patients with AL amyloidosis receiving stem cell transplantation.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood. 2002;99:731–5.

    Article  CAS  Google Scholar 

  2. Anagnostopoulos A, Aleman A, Ayers G, Donato M, Champlin R, Weber D, et al. Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma. Cancer. 2004;100:2607–12.

    Article  CAS  Google Scholar 

  3. Bayraktar UD, Bashir Q, Qazilbash M, Champlin RE, Ciurea SO. Fifty years of melphalan use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:344–56.

    Article  CAS  Google Scholar 

  4. Hari P, Aljitawi OS, Arce-Lara C, Nath R, Callander N, Bhat G, et al. A phase IIb, multicenter, open-label, safety, and efficacy study of high-dose, propylene glycol-free melphalan hydrochloride for injection (EVOMELA) for myeloablative conditioning in multiple myeloma patients undergoing autologous transplantation. Biol Blood Marrow Transplant. 2015;21:2100–5.

    Article  CAS  Google Scholar 

  5. Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study. Chest. 2005;128:1674–81.

    Article  CAS  Google Scholar 

  6. Badar T, Hari P, Chhabra S, Dhakal B, Drobyski WR, Fenske TS, et al. Use of propylene glycol-free melphalan conditioning in light-chain amyloidosis patients undergoing autologous hematopoietic cell transplantation is well tolerated and effective. Bone Marrow Transplant. 2018;53:1210–13. https://doi.org/10.1038/s41409-018-0178-5. Epub 2018.

    Article  CAS  Google Scholar 

  7. Sidiqi MH, Aljama MA, Buadi FK, Warsame RM, Lacy MQ, Dispenzieri A, et al. Stem cell transplantation for light chain amyloidosis: decreased early mortality over time. J Clin Oncol. 2018;36:1323–9.

    Article  Google Scholar 

  8. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, et al. 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. 2012;30:4541–9.

    Article  CAS  Google Scholar 

  9. Aljitawi OS, Ganguly S, Abhyankar SH, Ferree M, Marks R, Pipkin JD, et al. Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and alkeran in multiple myeloma autologous transplantation. Bone Marrow Transplant. 2014;49:1042–5.

    Article  CAS  Google Scholar 

  10. Singh R, Chen J, Miller T, Bergren M, Mallik R. Solution stability of Captisol-stabilized melphalan (Evomela) versus Propylene glycol-based melphalan hydrochloride injection. Pharm Dev Technol. 2016;14:1–6. https://doi.org/10.1080/10837450.2016.1265557. [Epub ahead of print].

    Article  Google Scholar 

  11. Koltun M, Morizzi J, Katneni K, Charman SA, Shackleford DM, McIntosh MP. Preclinical comparison of intravenous melphalan pharmacokinetics administered in formulations containing either (SBE)7 m-beta-cyclodextrin or a co-solvent system. Biopharm Drug Dispos. 2010;31:450–4.

    Article  CAS  Google Scholar 

  12. Desmaris RP, Mercier L, Paci A. Stability of melphalan in 0.9% sodium chloride solutions prepared in polyvinyl chloride bags for intravenous injection. Drugs R D. 2015;15:253–9.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA

    M. Hasib Sidiqi, Mohammed A. Aljama, Eli Muchtar, Francis K. Buadi, Rahma Warsame, Martha Q. Lacy, Angela Dispenzieri, David Dingli, Nelson Leung, Wilson I. Gonsalves, Prashant Kapoor, Taxiarchis V. Kourelis, William J. Hogan, Shaji K. Kumar & Morie A. Gertz

  2. Division of Nephrology, Department of Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA

    Nelson Leung

  3. Department of Pharmacy, Mayo Clinic Rochester, Rochester, MN, USA

    Robert C. Wolf

Authors
  1. M. Hasib Sidiqi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed A. Aljama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eli Muchtar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francis K. Buadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rahma Warsame
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martha Q. Lacy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Angela Dispenzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David Dingli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nelson Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wilson I. Gonsalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Prashant Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Taxiarchis V. Kourelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. William J. Hogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Robert C. Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shaji K. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Morie A. Gertz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Morie A. Gertz.

Ethics declarations

Conflict of interest

MAG received consultancy from Millenium and honoraria from Celgene, Millenium, Onyx, Novartis, SmithKline, Prothena, Ionis, and Amgen. SKK received consultancy from Celgene, Millennium, Onyx, Janssen, and BMS and research funding from Celgene, Millennium, Novartis, Onyx AbbVie, Janssen, and BMS. MQL received research funding from Celgene. DD received research funding from Karyopharm Therapeutics, and Millenium Pharmaceuticals. PK received research funding from Takeda, Celgene, and Amgen. AD received research funding from Celgene, Millennium, Pfizer, and Janssen and travel grant from Pfizer. The remaining authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sidiqi, M.H., Aljama, M.A., Muchtar, E. et al. Safety and efficacy of propylene glycol-free melphalan as conditioning in patients with AL amyloidosis undergoing stem cell transplantation. Bone Marrow Transplant 54, 1077–1081 (2019). https://doi.org/10.1038/s41409-018-0388-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-018-0388-x

Search

Advanced search

Quick links