Mel-200 Or Mel-140 , Which One İs More Advantageous? Retrospectively Analysis Of The Multiple Myeloma Patients Treated With Autologous Hematopoetic Stem Cell Transplantation

Year 2023, Volume: 5 Issue: 2, 92 - 98, 29.04.2023

Fazıl Cagrı Hunutlu , Fahir Özkalemkaş , Vildan Gürsoy , Vildan Ozkocaman

https://doi.org/10.46310/tjim.1223288

Abstract

Background Autologous hematopoietic stem cell transplantation (AHSCT) is one of the standard treatment modalities for patients with multiple myeloma (MM) under 65 years of age. Renal failure, significant disease comorbidity, significantly affects treatment choices. There are conflicting data in the literature regarding the dose of melphalan to be used for AHSCT in patients with renal failure and comorbid conditions. This study aimed to compare the efficacy and side effect data of different melphalan doses in patients with renal failure.
Material and Methods The study included 107 patients older than 18 years of age with a diagnosis of MM who underwent AHSCT in our center between January 2010 and January 2019. The data of the patients were analyzed retrospectively. Patients were grouped according to estimated glomerular filtration rate (eGFR: <60 or ≥60 mL/min) and melphalan doses (140-200). In addition to renal failure, patients with low-performance scores (ECOG 3 and above) or severe systemic comorbid disease were included in the Mel-140 group.
Results Comparative analysis of MEL-140 and MEL-200 doses used for AHSCT showed no significant difference between the two groups regarding side effects, disease-free survival, and overall survival. Engraftment times were similar in both groups. When the patients were analyzed according to eGFR level, the incidence and severity of mucositis were higher in the group with low eGFR levels (p=0.016). The duration of engraftment, complication with a febrile neutropenic attack, and development of septic shock were similar in both groups.
Conclusions In addition to renal failure, MEL-140 emerges as a preferable transplant preparation regimen considering its efficacy and side effect profile in patients with low-performance scores or severe systemic comorbidities.

Keywords

autologous hematopoietic stem cell transplantation, melphalan, renal failure, multiple myeloma

References

• Turkish Society of Hematology Multiple Myeloma Guidebook Version 1.03. İstanbul: Uniform; 2020.
• Pettengell R, Morgenstern GR, Woll PJ, Chang J, Rowlands M, Young R, Radford JA, Scarffe JH, Testa NG, Crowther D. Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis. Blood. 1993 Dec 15;82(12):3770-7.
• Dimopoulos MA, Sonneveld P, Leung N, Merlini G, Ludwig H, Kastritis E, Goldschmidt H, Joshua D, Orlowski RZ, Powles R, Vesole DH, Garderet L, Einsele H, Palumbo A, Cavo M, Richardson PG, Moreau P, San Miguel J, Rajkumar SV, Durie BG, Terpos E. International Myeloma Working Group Recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016 May 1;34(13):1544-57. doi: 10.1200/JCO.2015.65.0044.
• Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-20. doi: 10.1056/NEJMoa1611750.
• Badros A, Barlogie B, Siegel E, Roberts J, Langmaid C, Zangari M, Desikan R, Shaver MJ, Fassas A, McConnell S, Muwalla F, Barri Y, Anaissie E, Munshi N, Tricot G. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol. 2001 Sep;114(4):822-9. doi: 10.1046/j.1365-2141.2001.03033.x.
• St Bernard R, Chodirker L, Masih-Khan E, Jiang H, Franke N, Kukreti V, Tiedemann R, Trudel S, Reece D, Chen CI. Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure. Bone Marrow Transplant. 2015 Jan;50(1):95-9. doi: 10.1038/bmt.2014.226.
• Selby PJ, McElwain TJ, Nandi AC, Perren TJ, Powles RL, Tillyer CR, Osborne RJ, Slevin ML, Malpas JS. Multiple myeloma treated with high dose intravenous melphalan. Br J Haematol. 1987 May;66(1):55-62. doi: 10.1111/j.1365-2141.1987.tb06890.x.
• Cunningham D, Paz-Ares L, Milan S, Powles R, Nicolson M, Hickish T, Selby P, Treleavan J, Viner C, Malpas J, et al. High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma. J Clin Oncol. 1994 Apr;12(4):759-63. doi: 10.1200/JCO.1994.12.4.759.
• Sarosy G, Leyland-Jones B, Soochan P, Cheson BD. The systemic administration of intravenous melphalan. J Clin Oncol. 1988 Nov;6(11):1768-82. doi: 10.1200/JCO.1988.6.11.1768.
• Alberts DS, Chang SY, Chen HS, Moon TE, Evans TL, Furner RL, Himmelstein K, Gross JF. Kinetics of intravenous melphalan. Clin Pharmacol Ther. 1979 Jul;26(1):73-80. doi: 10.1002/cpt197926173.
• Bosanquet AG, Gilby ED. Pharmacokinetics of oral and intravenous melphalan during routine treatment of multiple myeloma. Eur J Cancer Clin Oncol. 1982 Apr;18(4):355-62. doi: 10.1016/0277-5379(82)90006-2.
• Osterborg A, Ehrsson H, Eksborg S, Wallin I, Mellstedt H. Pharmacokinetics of oral melphalan in relation to renal function in multiple myeloma patients. Eur J Cancer Clin Oncol. 1989 May;25(5):899-903. doi: 10.1016/0277-5379(89)90138-7..
• Auner HW, Iacobelli S, Sbianchi G, Knol-Bout C, Blaise D, Russell NH, Apperley JF, Pohlreich D, Browne PV, Kobbe G, Isaksson C, Lenhoff S, Scheid C, Touzeau C, Jantunen E, Anagnostopoulos A, Yakoub-Agha I, Tanase A, Schaap N, Wiktor-Jedrzejczak W, Krejci M, Schönland SO, Morris C, Garderet L, Kröger N. Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party. Haematologica. 2018 Mar;103(3):514-21. doi: 10.3324/haematol.2017.181339.
• Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Byrd JC, Czuczman MS, Fayad L, Forero A, Glenn MJ, Gockerman JP, Gordon LI, Harris NL, Hoppe RT, Horwitz SM, Kaminski MS, Kim YH, Lacasce AS, Mughal TI, Nademanee A, Porcu P, Press O, Prosnitz L, Reddy N, Smith MR, Sokol L, Swinnen L, Vose JM, Wierda WG, Yahalom J, Yunus F. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010 Mar;8(3):288-334. doi: 10.6004/jnccn.2010.0021.
• Augeul-Meunier K, Chretien ML, Stoppa AM, Karlin L, Benboubker L, Diaz JMT, Mohty M, Yakoub-Agha I, Bay JO, Perrot A, Bulabois CE, Huynh A, Mercier M, Frenzel L, Avet-Loiseau H, de Latour RP, Cornillon J. Extending autologous transplantation as first line therapy in multiple myeloma patients with severe renal impairment: a retrospective study by the SFGM-TC. Bone Marrow Transplant. 2018 Jun;53(6):749-755. doi: 10.1038/s41409-018-0122-8.
• Munshi PN, Vesole D, Jurczyszyn A, Zaucha JM, St Martin A, Davila O, Agrawal V, Badawy SM, Battiwalla M, Chhabra S, Copelan E, Kharfan-Dabaja MA, Farhadfar N, Ganguly S, Hashmi S, Krem MM, Lazarus HM, Malek E, Meehan K, Murthy HS, Nishihori T, Olin RL, Olsson RF, Schriber J, Seo S, Shah G, Solh M, Tay J, Kumar S, Qazilbash MH, Shah N, Hari PN, D'Souza A. Age no bar: A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma. Cancer. 2020 Dec 1;126(23):5077-87. doi: 10.1002/cncr.33171.
• Grazziutti ML, Dong L, Miceli MH, Krishna SG, Kiwan E, Syed N, Fassas A, van Rhee F, Klaus H, Barlogie B, Anaissie EJ. Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model. Bone Marrow Transplant. 2006 Oct;38(7):501-6. doi: 10.1038/sj.bmt.1705471.
• Tricot G, Alberts DS, Johnson C, Roe DJ, Dorr RT, Bracy D, Vesole DH, Jagannath S, Meyers R, Barlogie B. Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res. 1996 Jun;2(6):947-52.
• Hussain S, Browne R, Chen J, Parekh S. Lenalidomide-induced severe hepatotoxicity. Blood. 2007 Nov 15;110(10):3814. doi: 10.1182/blood-2007-06-097758.
• Zanella MC, Rubbia-Brandt L, Giostra E, Chalandon Y, Hadengue A, Spahr L. A case of drug-ınduced hepatitis due to lenalidomide. Case Rep Gastroenterol. 2011 Apr 13;5(1):217-22. doi: 10.1159/000326935.
• Jain P. Lenalidomide-induced acute liver failure. Blood Transfus. 2009 Oct;7(4):335-6; author reply 337. doi: 10.2450/2009.0086-09.
• Hussein MA. Lenalidomide: patient management strategies. Semin Hematol. 2005 Oct;42(4 Suppl 4):S22-5. doi: 10.1053/j.seminhematol.2005.10.003.