Multiple Myeloma Treatment Guidelines by the Portuguese Group of Multiple Myeloma
DOI:
https://doi.org/10.20344/amp.19037Keywords:
Multiple Myeloma/drug therapy, PortugalAbstract
The treatment of multiple myeloma has profoundly changed with the introduction of several innovative therapies. The optimization of therapeutic sequencing through the combined use of the various drugs developed in recent years and the attention given to the characteristics of patients have allowed the reduction of toxicities and increased survival and quality of life of patients with multiple myeloma. These treatment recommendations from the Portuguese Multiple Myeloma Group offer guidance for first-line treatment and progression/relapse situations. These recommendations are given highlighting the data that justify each choice and referring to the respective levels of evidence that support these options. Whenever possible, the respective national regulatory framework is presented. These recommendations constitute an advance towards the best treatment of multiple myeloma in Portugal.
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References
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122-8.
Binder M, Nandakumar B, Rajkumar SV, Kapoor P, Buadi FK, Dingli D, et al. Mortality trends in multiple myeloma after the introduction of novel therapies in the United States. Leukemia. 2022;36:801-8.
Callander NS, Baljevic M, Adekola K, Anderson LD, Campagnaro E, Castillo JJ, et al. NCCN Guidelines® Insights: multiple myeloma, version 3.2022. J Natl Compr Canc Netw. 2022;20:8-19.
Sive J, Cuthill K, Hunter H, Kazmi M, Pratt G, Smith D, et al. Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum Guideline. Br J Haematol. 2021;193:245-68.
Moreau P, Kumar SK, Miguel JS, Davies F, Zamagni E, Bahlis N, et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol. 2021;22:e105-18.
Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Hemasphere. 2021;5:e528.
Munshi NC, Avet-Loiseau H, Anderson KC, Neri P, Paiva B, Samur M, et al. A large meta-analysis establishes the role of MRD negativity in longterm survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4:5988-99.
Gertz MA, Dingli D. How we manage autologous stem cell transplantation for patients with multiple myeloma. Blood. 2014;124:882-90.
Sonneveld P, Goldschmidt H, Rosiñol L, Bladé J, Lahuerta JJ, Cavo M, et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013;31:3279-87.
Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: The GRIFFIN trial. Blood. 2020;136:936-45.
Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29-38.
Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: Results of the prospective IFM2013-04 trial. Blood. 2016;127:2569-74.
Leiba M, Kedmi M, Duek A, Freidman T, Weiss M, Leiba R, et al. Bortezomib-Cyclophosphamide-Dexamethasone (VCD) versus Bortezomib-Thalidomide-Dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br J Haematol. 2014;166:702-10.
Gay F, Cerrato C, Petrucci MT, Zambello R, Gamberi B, Ballanti S, et al. Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: results from the FORTE trial. J Clin Oncol. 2019;37:8002.
Costa LJ, Chhabra S, Godby KN, Medvedova E, Cornell RF, Hall AC, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) induction, autologous transplantation and post-transplant, response-adapted, measurable residual disease (MRD)-based darakrd consolidation in patients with newly diagnosed multiple myeloma (NDMM). Blood. 2019;134:S860.
Leypoldt LB, Besemer B, Asemissen AM, Hänel M, Blau IW, Görner M, et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial. Leukemia. 2022;36:885-8.
Gonsalves WI, Buadi FK, Ailawadhi S, Bergsagel PL, Chanan Khan AA, Dingli D, et al. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus statement. Bone Marrow Transplant. 2019;54:353-67.
Marini C, Maia T, Bergantim R, Pires J, Aguiar E, Guimarães JE, et al. Real-life data on safety and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma. Ann Hematol. 2019;98:369-79.
Dhakal B, Nelson A, Guru Murthy GS, Fraser R, Eastwood D, Hamadani M, et al. Autologous hematopoietic cell transplantation in patients with multiple myeloma: effect of age. Clin Lymphoma Myeloma Leuk. 2017;17:165-72.
Saad A, Mahindra A, Zhang MJ, Zhong X, Costa LJ, Dispenzieri A, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2014;20:402-8.e1.
Chakraborty R, Muchtar E, Kumar SK, Buadi FK, Dingli D, Dispenzieri A, et al. Impact of pre-transplant bone marrow plasma cell percentage on post-transplant response and survival in newly diagnosed multiple myeloma. Leuk Lymphoma. 2017;58:308-15.
Vij R, Kumar S, Zhang MJ, Zhong X, Huang J, Dispenzieri A, et al. Impact of pretransplant therapy and depth of disease response before autologous transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2015;21:335-41.
Rosiñol L, García-Sanz R, Lahuerta JJ, Hernández-García M, Granell M, de la Rubia J, et al. Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease. Haematologica. 2012;97:616-21.
Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, et al. Response adapted induction treatment improves outcomes for myeloma patients; results of the phase III myeloma XI study. Blood. 2016;128:244.
Uy GL, Costa LJ, Hari PN, Zhang MJ, Huang JX, Anderson KC, et al. Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation. Bone Marrow Transplant. 2015;50:1513-8.
Mohty M, Hübel K, Kröger N, Aljurf M, Apperley J, Basak GW, et al. Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2014;49:865-72.
Giralt S, Costa L, Schriber J, DiPersio J, Maziarz R, McCarty J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Bio Blood Marrow Transplant. 2014;20:295-308.
Bodge MN, Reddy S, Thompson MS, Savani BN. Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic kidney disease: analysis of the literature and recommendations. Bio Blood Marrow Transplant. 2014;20:908-19.
Muchtar E, Dingli D, Kumar S, Buadi FK, Dispenzieri A, Hayman SR, et al. Autologous stem cell transplant for multiple myeloma patients 70 years or older. Bone Marrow Transplant. 2016;51:1449-55.
Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, et al. Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020;7:e456–68.
Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, et al. Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol. 2019;37:589-97.
McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. New Eng J Med. 2012;366:1770-81.
Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:1378-90.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. New Eng J Med. 2012;366:1782-91.
McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279-89.
Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, et al. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018;32:383-90.
Gregersen H, Peceliunas V, Remes K, Schjesvold F, Abildgaard N, Nahi H, et al. Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: a randomised phase 2 trial by the Nordic Myeloma Study Group. Eur J Haematol. 2022;108:34-44.
Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019;393:253-64.
Dimopoulos MA, Rajkumar SV, Lonial S, Chng WJ, Iida S, Mateos MV, et al. Interim analyses of overall survival (OS) from the TOURMALINE MM3 & MM4 studies of ixazomib maintenance following primary therapy in multiple myeloma (MM). Blood. 2021;138:S1656.
Zhang S, Kulkarni AA, Xu B, Chu H, Kourelis T, Go RS, et al. Bortezomibbased consolidation or maintenance therapy for multiple myeloma: a meta-analysis. Blood Cancer J. 2020;10:33.
Sonneveld P, Schmidt-Wolf IG, van der Holt B, el Jarari L, Bertsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012;30:2946-55.
Rosiñol L, Oriol A, Teruel AI, de la Guía AL, Blanchard M, de la Rubia J, et al. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017;31:1922-7.
Holstein SA, Suman VJ, Hillengass J, McCarthy PL. Future directions in maintenance therapy in multiple myeloma. J Clin Med. 2021;10:2261.
Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:1582-96.
Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395:132-41.
Antunes L, Rocha-Gonçalves F, Chacim S, Lefèvre C, Pereira M, Pereira S, et al. Real-world treatment patterns, resource use and cost burden of multiple myeloma in Portugal. Eur J Cancer Care. 2019;28:e13026.
MacEwan JP, Batt K, Yin W, Peneva D, Sison S, Vine S, et al. Economic burden of multiple myeloma among patients in successive lines of therapy in the United States. Leuk Lymphoma. 2017;59:941-9.
Bergantim R, João C, Geraldes C, Neves M, Trigo F, Neves M, et al. Multiple myeloma in Portugal: incidence, prevalence, mortality and treatment pattern. European Hematology Association; 2020. [consultado 2022 ago 21]. Disponível em: https://library.ehaweb.org/eha/2020/eha25th/297938/rui.bergantim.multiple.myeloma.in.portugal.incidence.prevalence.mortality.and.html?f=listing=0*browseby=8*sortby=1*search=MULTIPLE+MYELOMA+IN+PORTUGAL:+INCIDENCE,+PREVALENCE,+MORTALITY+AND+TREATMENT+PATTERN.
Yong K, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-Mcquire S, et al. Multiple myeloma: patient outcomes in real-world practice. Br J Haematol. 2016;175:252-64.
Michaelis LC, Saad A, Zhong X, Le-Rademacher J, Freytes CO, Marks DI, et al. Salvage second hematopoietic cell transplantation in myeloma. Biol Blood Marrow Transplant. 2013;19:760-6.
Lemieux C, Muffly LS, Iberri DJ, Craig JK, Johnston LJ, Lowsky R, et al. Outcomes after delayed and second autologous stem cell transplant in patients with relapsed multiple myeloma. Bone Marrow Transplant. 2021;56:2664-71.
Dhakal B, D’souza A, Kleman A, Chhabra S, Mohan M, Hari P. Salvage second transplantation in relapsed multiple myeloma HHS public access. Leukemia. 2021;35:1214-7.
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. New Eng J Medicine. 2015;372:142-52.
Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. New Eng J Med. 2016;374:1621-34.
Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, et al. Daratumumab plus lenalidomide and dexamethasone inrelapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020;34:1875-84.
Dimopoulos MA, Lonial S, White D, Moreau P, Palumbo A, San-Miguel J, et al. Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and posthoc analyses on progression-free survival and tumour growth. Br J Haematol. 2017;178:896-905.
Bal S, Malek E, Kansagra A, Usmani SZ, Vij R, Godby KN, et al. Treatment outcomes of triple class refractory multiple myeloma: a benchmark for new therapies. Leukemia. 2022;36:877-80.
Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:801-12.
Richardson PG, Perrot A, San-Miguel J, Beksac M, Spicka I, Leleu X, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022;23:416-27.
Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019;394:2096-107.
Lakshman A, Singh PP, Rajkumar SV, Dispenzieri A, Lacy MQ, Gertz MA, et al. Efficacy of VDT PACE-like regimens in treatment of relapsed/ refractory multiple myeloma. Am J Hematol. 2018;93:179-86.
Goldsmith SR, Fiala MA, Wang B, Schroeder MA, Wildes TM, Ghobadi A, et al. DCEP and bendamustine/prednisone as salvage therapy for quadand penta-refractory multiple myeloma. Ann Hematol. 2020;99:1041-8.
Rivell GL, Brunson CY, Milligan L, Stuart RK, Costa LJ. Effectiveness and safety of high-dose cyclophosphamide as salvage therapy for high-risk multiple myeloma and plasma cell leukemia refractory to new biological agents. Am J Hematol. 2011;86;699-701.
Lonial S, Berdeja JG, Dimopoulos MA, Jagannath S, Knop S, Quach H, et al. P-203: EXCALIBER: a phase 3 study comparing iberdomide, daratumumab, and dexamethasone (IberDd) with daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2021;21:S150.
Charlí Nski G, Vesole DH, Jurczyszyn A, Ailawadhi S. Rapid progress in the use of immunomodulatory drugs and cereblon E3 ligase modulators in the treatment of multiple myeloma. Cancers. 2021;13:4666.
Richardson PG, Vangsted AJ, Ramasamy K, Trudel S, Martínez J, Mateos MV, et al. First-in-human phase I study of the novel CELMoD agent CC-92480 combined with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2020;38:S8500.
Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384:705-16.
Berdeja JG, Madduri D, Usmani SZ,. Jakubowiak A, Agha M, Cohen AD, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398:314-24.
Cho SF, Yeh TJ, Anderson KC, Tai YT. Bispecific antibodies in multiple myeloma treatment: a journey in progress. Front Oncol. 2022;12:1032775.
Moreau P, Garfall AL, van de Donk NW, Nahi H, San-Miguel JF, Oriol A, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387:495-505.
de Oca RM, Alavi AS, Vitali N, Bhattacharya S, Blackwell C, Patel K, et al. Belantamab mafodotin (GSK2857916) drives immunogenic cell death and immune-mediated antitumor responses in vivo. Mol Cancer Ther. 2021;20:1941-55.
Vogl DT, Kaufman JL, Holstein SA, Atrash S, Nadeem O, Janakiram M, et al. Modakafusp alfa (TAK-573), an immunocytokine, shows clinical activity in patients with relapsed/refractory multiple myeloma; updated results from a first-in-human phase 1 study. Blood. 2021;138:S898.
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