Current role of minimal residual disease in plasma cell myeloma: Position of Polish Myeloma Consortium
Abstract
< strong > < /strong > Wprowadzenie do terapii szpiczaka plazmocytowego (PCM) znacznej liczby nowych leków pozwoliło na poprawę głębokości uzyskiwanych odpowiedzi, a w konsekwencji na wydłużenie okresu remisji i przeżycia chorych. Mimo wyższego obecnie odsetka całkowitych remisji (CR) u większości pacjentów dochodzi jednak do nawrotu choroby, co może być tłumaczone pozostawaniem po zakończeniu leczenia niewielkich populacji klonalnych plazmocytów w szpiku kostnym, określanych mianem minimalnej choroby resztkowej (MRD). Prognostyczne znaczenie występowania MRD u chorych w CR potwierdzono w wielu badaniach klinicznych, a ocena MRD stała się w ostatnim czasie rutynowym narzędziem w ocenie skuteczności najnowszych leków i schematów terapii. Ponadto w najnowszych kryteriach odpowiedzi IMWG (International Myeloma Working Group) z 2016 roku wprowadzono kategorie odpowiedzi oparte na badaniu MRD oznaczanej z czułością co najmniej 10–5 najnowocześniejszymi technikami diagnostycznymi — cytometrii przepływowej nowej generacji i sekwencjonowania nowej generacji. W pracy podsumowano aktualne znaczenie oceny MRD u chorych na PCM, ze szczególnym uwzględnieniem metodyki oceny MRD techniką cytometrii przepływowej. W opinii Polskiego Konsorcjum Szpiczakowego upowszechnienie i standaryzacja oceny MRD w PCM może się przyczynić do poprawy wyników leczenia chorych na ten nowotwór w Polsce.
Keywords: plasma cell myelomaminimal residual diseaseprognosis
References
- Wojciechowska U., Didkowska J. Zachorowania i zgony na nowotwory złośliwe w Polsce. 2017. http://onkologia.org.pl/raporty (14/03/2017).
- Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011; 364(11): 1046–1060.
- Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15(12): e538–e548.
- Dmoszyńska A, Usnarska-Zubkiewicz L, Walewski J, et al. Zalecenia Polskiej Grupy Szpiczakowej dotyczące rozpoznawania i leczenia szpiczaka plazmocytowego oraz innych dyskrazji plazmocytowych na rok 2017. Acta Haematol Pol. 2017; 48(2): 55–103.
- Didkowska J., Wojciechowska U., Zatoński W. Wskaźniki przeżyć chorych na nowotwory złośliwe w Polsce zdiagnozowanych w latach 2000-2002. 2009. http://onkologia.org.pl/publikacje (14/03/2017).
- Pulte D, Jansen L, Castro FA, et al. GEKID Cancer Survival Working Group. Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century. Br J Haematol. 2015; 171(2): 189–196.
- Pulte D, Redaniel MT, Lowry L, et al. Age disparities in survival from lymphoma and myeloma: a comparison between US and England. Br J Haematol. 2014; 165(6): 824–831.
- Kubiczkova L, Pour L, Sedlarikova L, et al. Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma. J Cell Mol Med. 2014; 18(6): 947–961.
- Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010; 24(1): 22–32.
- Sanchez L, Wang Y, Siegel DS, et al. Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma. J Hematol Oncol. 2016; 9(1): 51.
- Grabarska A, Dmoszyńska-Graniczka M, Nowosadzka E, et al. [Histone deacetylase inhibitors - molecular mechanisms of actions and clinical applications]. Postepy Hig Med Dosw (Online). 2013; 67: 722–735.
- Salomon-Perzyński A, Jamroziak K. The role of daratumumab in the treatment of relapsed/refractory plasma cell myeloma. Hematol. 2017; 8(4): 255–264.
- Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998; 102(5): 1115–1123.
- Chanan-Khan AA, Giralt S. Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol. 2010; 28(15): 2612–2624.
- Gay F, Larocca A, Wijermans P, et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2011; 117(11): 3025–3031.
- Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012; 120(9): 1801–1809.
- Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012; 119(19): 4375–4382.
- Durie BGM, Harousseau JL, Miguel JS, et al. International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006; 20(9): 1467–1473.
- Shain KH, Dalton WS. Environmental-mediated drug resistance: a target for multiple myeloma therapy. Expert Rev Hematol. 2009; 2(6): 649–662.
- Hajek R, Okubote SA, Svachova H. Myeloma stem cell concepts, heterogeneity and plasticity of multiple myeloma. Br J Haematol. 2013; 163(5): 551–564.
- Paiva B, Vidriales MB, Cerveró J, et al. GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Groups. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood. 2008; 112(10): 4017–4023.
- Martínez-López J, Paiva B, López-Anglada L, et al. Spanish Multiple Myeloma Group / Program for the Study of Malignant Blood Diseases Therapeutics (GEM / PETHEMA) Cooperative Study Group. Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality. Blood. 2015; 126(7): 858–862.
- Rajkumar SV, Harousseau JL, Durie B, et al. International Myeloma Workshop Consensus Panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011; 117(18): 4691–4695.
- Sanchez-Vega B, Ayala R, Cedena T, et al. Minimal residual disease testing for multiple myeloma. Hematol. 2017; 8(3): 219–227.
- Rihova L, Hajek R. Flow cytometric minimal residual disease assessment in multiple myeloma. Hematol. 2017; 8(3): 211–218.
- Rawstron AC, Child JA, de Tute RM, et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol. 2013; 31(20): 2540–2547.
- Paiva B, Gutiérrez NC, Rosiñol L, et al. PETHEMA/GEM (Programa para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma) Cooperative Study Groups. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood. 2012; 119(3): 687–691.
- Ferrero S, Ladetto M, Drandi D, et al. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival. Leukemia. 2015; 29(3): 689–695.
- Paiva B, Martinez-Lopez J, Vidriales MB, et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol. 2011; 29(12): 1627–1633.
- Paiva B, Chandia M, Puig N, et al. The prognostic value of multiparameter flow cytometry minimal residual disease assessment in relapsed multiple myeloma. Haematologica. 2015; 100(2): e53–e55.
- Rawstron AC, Gregory WM, de Tute RM, et al. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction. Blood. 2015; 125(12): 1932–1935.
- Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014; 123(20): 3073–3079.
- Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016; 17(8): e328–e346.
- Rawstron AC, Orfao A, Beksac M, et al. European Myeloma Network. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica. 2008; 93(3): 431–438.
- Paiva B, Almeida J, Pérez-Andrés M, et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom. 2010; 78(4): 239–252.
- Raja KRM, Kovarova L, Hajek R. Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders. Br J Haematol. 2010; 149(3): 334–351.
- Oldaker TA, Wallace PK, Barnett D. Flow cytometry quality requirements for monitoring of minimal disease in plasma cell myeloma. Cytometry B Clin Cytom. 2016; 90(1): 40–46.
- Flores-Montero J, de Tute R, Paiva B, et al. Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin Cytom. 2016; 90(1): 61–72.
- Stetler-Stevenson M, Paiva B, Stoolman L, et al. Consensus guidelines for myeloma minimal residual disease sample staining and data acquisition. Cytometry B Clin Cytom. 2016; 90(1): 26–30.
- Arroz M, Came N, Lin P, et al. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry B Clin Cytom. 2016; 90(1): 31–39.
- Flores-Montero J, Sanoja-Flores L, Paiva B, et al. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia. 2017; 31(10): 2094–2103.
- Krzywdzińska A, Solarska I, Puła B, et al. Minimal residual disease assessment in plasma cell myeloma patients in Poland: survey of the Polish Myeloma Consortium. Hematol. 2017; 8(4): 239–245.
- Zimmerman T, Raje NS, Vij R, et al. Final Results of a Phase 2 Trial of Extended Treatment (tx) with Carfilzomib (CFZ), Lenalidomide (LEN), and Dexamethasone (KRd) Plus Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (NDMM). Blood. 2016; 128(22): 675.
- Jakubowiak AJ, Raje N, Vij R, et al. High Rate of Sustained Minimal Residual Disease Negativity Predicts Prolonged Survival for the Overall Patient Population in the Phase 2 KRd Plus Autologous Stem Cell Transplantation MMRC Trial. Blood. 2017; 130(Suppl 1): 4533.
- Jamroziak K, Giannopoulos K, Wrobel T, et al. Preemptive Daratumumab Therapy for Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma: Rationale and Design of the Polish Myeloma Consortium Predator Study. Blood. 2017; 130(Suppl 1): 5404.
- Dimopoulos MA, Oriol A, Nahi H, et al. POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016; 375(14): 1319–1331.
- Nishihori T, Song J, Shain KH. Minimal Residual Disease Assessment in the Context of Multiple Myeloma Treatment. Curr Hematol Malig Rep. 2016; 11(2): 118–126.
![](https://journals.viamedica.pl/plugins/generic/popups/images/icons/close.png)