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Systemic Anti-Cancer Therapy Regimen Library

HSCT Autologous conditioning - melphalan 140

Treatment Overview

This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycle 1 - 60 days

Cycle length:
60

Hydration in addition to that specified is recommended as per institutional practice and may need an individualised approach.


melphalan:

  • Consider oral cryotherapy on Day -1 by giving patient ice to suck starting 15 minutes prior to, during and up to one hour after the melphalan infusion.
  • The total time from preparation to the completion of the infusion should not exceed 90 minutes.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from Day 5 until engraftment.

Cycle details

Cycle 1 - 60 days

Medication / Procedure Dose Route Days Max Duration
sodium chloride 0.9 % intravenous -1 120 minutes
melphalan 140 mg/m² intravenous -1 20 minutes
sodium chloride 0.9 % intravenous -1 120 minutes
paracetamol * 1000 mg flat dosing oral administration 0
proMETHazine * 12.5 mg intravenous 0 1 minutes
Autologous stem cell transplant intravenous 0
filgrastim 5 microgram/kg Once daily subcutaneous injection 5

Hydration in addition to that specified is recommended as per institutional practice and may need an individualised approach.


melphalan:

  • Consider oral cryotherapy on Day -1 by giving patient ice to suck starting 15 minutes prior to, during and up to one hour after the melphalan infusion.
  • The total time from preparation to the completion of the infusion should not exceed 90 minutes.

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from Day 5 until engraftment.

Full details

Cycle 1 - 60 days

Day: -1

Medication Dose Route Max duration Details
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to melphalan infusion.

melphalan 140 mg/m² intravenous 20 minutes
Instructions:
  • Consider oral cryotherapy by giving patient ice to suck starting 15 minutes prior to, during and up to one hour after the melphalan infusion.
  • The total time from preparation to the completion of the infusion should not exceed 90 minutes.
Additional details:
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After melphalan infusion.

Day: 0

Medication / Procedure Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

ONE hour prior to return of autologous stem cells, or as per institutional practice.

proMETHazine * 12.5 mg intravenous 1 minutes
Instructions:

ONE hour prior to return of autologous stem cells, or as per institutional practice.

Autologous stem cell transplant intravenous
Instructions:

Administer as per institutional practice, at least 24 hours after melphalan infusion completed.

Day: 5

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Give ONCE daily from Day 5 until engraftment.

  • Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Additional details

Section 1: Dosing for bodyweight

Supportive Care Factors

Factor Value
Antifungal prophylaxis: Routine antifungal prophylaxis recommended
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis recommended
Emetogenicity: High
Gastroprotection: Gastroprotection may be considered
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Irradiated blood components: Irradiation of blood components is recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis may be considered

References

Anagnostopoulos, A., Aleman, A., Ayers, G., et al.2004." Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma." Cancer Jun 15;100(12):2607-12., PMID: 15197803

Attal, M., J. L. Harousseau, A. M. Stoppa, et al. 1996. "A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome." N.Engl.J.Med. 335(2):91-97., PMID: 8649495

Barlogie B, Kyle RA, Anderson KC et al. 2008." Standard chemotherapy compared with high dose chemoradiotherapy for multiple myeloma: Final results of a phase III US Intergroup trial S9321."J Clin Oncol. 24:929-36., PMID: 16432076

Bensinger, W. I., P. S. Becker, T. A. Gooley, et al. 2016. "A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT." Bone Marrow Transplant 51(1):67-71., PMID: 26367217

Blade J, Rosignol L, Sureda A et al. 2005. "PETHEMA. High dose therapy intensification compared with continuous standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: Long term results from a prospective randomised trial from the Spanish co-operative group PETHEMA" Blood 106:3755-9, PMID: 16105975

Child, J. A., G. J. Morgan, F. E. Davies, et al. 2003. "High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma." N.Engl.J.Med. 348(19):1875-1883., PMID: 12736280

El Fakih, R., P. Fox, U. Popat, et al. 2015. "Autologous Hematopoietic Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients." Clin Lymphoma Myeloma Leuk 15(8):472-476, PMID: 25963284

Fenk, R, P Schneider, M Kropff, et al. 2005. "High-dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment-related mortality in patients with multiple myeloma: results of a randomised study." British journal of haematology 130(4):588-594., PMID: 16098074

Fernand JP, Katsahian S, Divine M et al. 2005."High dose therapy and autologous blood stem cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65, Long term results of a randomised trial from the MAG"J Clin Oncol. 23:9227-33., PMID: 16275936

Gay, F., S. Oliva, M. T. Petrucci, et al. 2015. "Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial." Lancet Oncol 16(16):1617-1629, PMID: 26596670

Gertz MA, Lacy MQ, Dispenzieri A et al. 2004 "Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate." Bone Marrow Transplant.34:1025-31., PMID: 15516945

Koreth J, Cutler CS, Djulbegovic B et al. 2007 " High-dose therapy with single autologous transplant versus chemotherapy for newly-diagnosed multiple myeloma. A systematic review and meta-analysis of randomised controlled trials". Biol Blood Marrow Transplant. 13:183-96., PMID: 17241924

Levy V, Katsehian S, Fernand JP et al. 2005 "A meta-analysis of data from 575 patients with multiple myeloma randomly assigned to either high-dose therapy or conventional therapy". Medicine (Baltimore) ;84:250-60., PMID: 16010209

Moreau, P., T. Facon, M. Attal, et al. 2002. "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. 99(3):731-735., PMID: 11806971

Palumbo A, Cavallo F, Gay F, et al. 2014” Autologous transplantation and maintenance therapy in multiple myeloma “ N Engl J Med 371 (10) 895-905., PMID: 25184862

Perfetti V, Siena S, Palladini G et al. 2006 "Long-term results of a risk-adapted approach to conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis. Haematologica." 91:1635-43., PMID: 17145600

Skinner M, Sanchorawala V, Seldin DC et al. 2004 "High-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis: An 8-year study. Ann Intern Med". 140:85-93., PMID: 14734330

Bubalo J, Carpenter PA, et al; American Society for Blood and Marrow Transplantation practice guideline committee. Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee. Biol Blood Marrow Transplant. 2014 May;20(5):600-16. doi: 10.1016/j.bbmt.2014.01.019. Epub 2014 Jan 23., PMID: 24462742

Correa MEP, Cheng KKF, Chiang K, Kandwal A, Loprinzi CL, Mori T, Potting C, Rouleau T, Toro JJ, Ranna V, Vaddi A, Peterson DE, Bossi P, Lalla RV, Elad S. Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2020 May;28(5):2449-2456. doi: 10.1007/s00520-019-05217-x. Epub 2019 Dec 14., PMID: 31836937

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

New Zealand Blood Service Transfusion Medicine Handbook Third Edition, 2016 https://www.nzblood.co.nz/assets/Transfusion-Medicine/PDFs/111G122.pdf (accessed 16 June 2022).

Doyle J, Raggatt M, Slavin M, McLachlan SA, Strasser SI, Sasadeusz JJ, Howell J, Hajkowicz K, Nandurkar H, Johnston A, Bak N, Thompson AJ. Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement. Med J Aust. 2019 Jun;210(10):462-468. doi: 10.5694/mja2.50160. Epub 2019 May 19., PMID: 31104328

Nakagaki M, Button E, Keating A, Marsh J, Mitchell C, Birchley A, Kennedy GA. Hyperhydration is not necessary for high-dose melphalan in stem cell transplantation. Bone Marrow Transplant. 2020 Apr;55(4):827-829. doi: 10.1038/s41409-019-0586-1. Epub 2019 Jun 11. , PMID: 31186515

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.