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se다발골수종에서 측정가능잔존질환 검사법의 현황과 발전방향

Measurable Residual Disease of Multiple Myeloma: Current Methods and Future Directions

Hwang Sang Mee|Lee Youngeun
대한진단검사의학회 (Korean Society For Laboratory Medicine)|2024.07|Laboratory Medicine Online|제14권 제3호|pp. 155-162|DOI 10.47429/lmo.2024.14.3.155

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Flow cytometryNext-generation sequencingMultiple myelomaMeasurable residual disease

초록

다발골수종에서 측정가능잔존질환의 검출은 환자의 예후에 상당한 영향을 미친다. 다발골수종의 치료 과정에 신약과 조혈모세포이식이 도입되면서 반응 평가에서 완전 관해 비율이 과거에 비해 증가하였지만, 완전 관해에 이른 환자 중 상당수가 재발을 경험한다. 재발 가능성이 높은 고위험군 환자를 조기에 발견하기 위해서는 기존보다 더 깊은 반응 단계까지 평가해야 한다. 여러 연구에서, 전통적인 검사법에 비해 훨씬 더 민감한 검사법을 사용하여 측정가능잔존질환을 검출하였을 때 음성으로 평가받은 환자들이 분명한 예후 개선 효과를 보였다고 보고하였다. 따라서 10-5 이하의 잔존질환까지 측정할 수 있는 민감한 검사법이 여러 임상시험에도 포함되었다. 본 종설에서는 다발골수종에서 유세포분석법과 차세대염기서열분석 기반의 매우 민감한 측정가능잔존질환 검사에 초점을 맞추어 기술하고자 한다. 다발골수종에서 현재 적용되고 있는 잔존질환 측정 검사법의 종류, 각 검사법의 구체적인 특성 및 검사법 간 차이에서 비롯되는 이질성을 극복하기 위하여 시도되고 있는 측정방법 일치화 전략에 대해 기술하였다. 또 다발골수종의 잔존질환 검출 분야에서 향후 추가적인 연구를 요하는 주제에 대해서도 언급하였다.

Abstract

The detection of measurable residual disease (MRD) has a significant impact on the prognosis of patients with multiple myeloma (MM). While complete response rates have increased due to the discovery of novel agents and hematopoietic stem cell transplantation, a significant number of patients experience relapse after achieving a complete response. Therefore, it is necessary to evaluate the deeper response to identify patients who are at a higher risk of early relapse. Patients who achieve MRD negativity through highly sensitive MRD assays have shown improved survival. Moreover, MRD assays with sensitivities greater than 10-5 have been included in various clinical trials. This review focuses on high-sensitivity flow cytometry and next-generation sequencing (NGS)-based MRD in MM. In this article, the current MRD approaches in MM have been summarized, considering the specific characteristics of each assay and harmonization to overcome substantial heterogeneity. Furthermore, we discuss the issues in MM MRD that require further investigation.

참고문헌 (50)

  1. Kumar S, "International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma", Lancet Oncol, 17, pp.e328~e346 (2016)
  2. Paiva B, "New criteria for response assessment : role of minimal residual disease in multiple myeloma", Blood, 125, pp.3059~3068 (2015)
  3. Paiva B, "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, 119, pp.687~691 (2012)
  4. Yee AJ, "Minimal residual disease in multiple myeloma : why, when, where", Hematology Am Soc Hematol Educ Program, 2021, pp.37~45 (2021)
  5. Munshi NC, "A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma", Blood Adv, 4, pp.5988~5999 (2020)
  6. San Miguel JF, "Immunophenotypic evaluation of the plasma cell compartment in multiple myeloma : a tool for comparing the efficacy of different treatment strategies and predicting outcome", Blood, 99, pp.1853~1856 (2002)
  7. Puig N, "Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry", Leukemia, 28, pp.391~397 (2014)
  8. Bakkus MH, "Post-transplantation tumour load in bone marrow, as assessed by quantitative ASO-PCR, is a prognostic parameter in multiple myeloma", Br J Haematol, 126, pp.665~674 (2004)
  9. Flores-Montero J, "Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma", Leukemia, 31, pp.2094~2103 (2017)
  10. Ladetto M, "Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders", Leukemia, 28, pp.1299~1307 (2014)
  11. Takamatsu H, "Comparison of minimal residual disease detection by multiparameter flow cytometry, ASO-qPCR, droplet digital PCR, and deep sequencing in patients with multiple myeloma who underwent autologous stem cell transplantation", J Clin Med, 6, pp.91~ (2017)
  12. Costa LJ, "International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials", Leukemia, 35, pp.18~30 (2021)
  13. Maclachlan KH, "Minimal residual disease in multiple myeloma : defining the role of next generation sequencing and flow cytometry in routine diagnostic use", Pathology, 53, pp.385~399 (2021)
  14. Roshal M, "MRD detection in multiple myeloma : comparison between MSKCC 10-color single-tube and EuroFlow 8-color 2-tube methods", Blood Adv, 1, pp.728~732 (2017)
  15. Blum A, "Standardized assay for assessment of minimal residual disease in blood, bone marrow and apheresis from patients with plasma cell myeloma", Sci Rep, 9, pp.2922~ (2019)
  16. Bayly E, "Validation of a modified pre-lysis sample preparation technique for flow cytometric minimal residual disease assessment in multiple myeloma, chronic lymphocytic leukemia, and B-non Hodgkin lymphoma", Cytometry B Clin Cytom, 98, pp.385~398 (2020)
  17. Soh KT, "Evaluation of multiple myeloma measurable residual disease by high sensitivity flow cytometry : an international harmonized approach for data analysis", Cytometry B Clin Cytom, 102, pp.88~106 (2022)
  18. Muz B, "A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma", Br J Haematol, 173, pp.70~81 (2016)
  19. Oberle A, "Long-term CD38 saturation by daratumumab interferes with diagnostic myeloma cell detection", Haematologica, 102, pp.e368~e370 (2017)
  20. Courville EL, "VS38 identifies myeloma cells with dim CD38 expression and plasma cells following daratumumab therapy, which interferes with CD38 detection for 4 to 6 months", Am J Clin Pathol, 153, pp.221~228 (2020)
  21. Rai S, "Utility of CD229 as novel marker in measurable residual disease assessment in multiple myeloma-An evidence-based approach", Int J Lab Hematol, 45, pp.179~186 (2023)
  22. Soh KT, "CD319 (SLAMF7) an alternative marker for detecting plasma cells in the presence of daratumumab or elotuzumab", Cytometry B Clin Cytom, 100, pp.497~508 (2021)
  23. Ching T, "Analytical evaluation of the clonoSEQ Assay for establishing measurable(minimal)residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma", BMC Cancer, 20, pp.612~ (2020)
  24. Dunn-Walters D, "Immunoglobulin gene analysis as a tool for investigating human immune responses", Immunol Rev, 284, pp.132~147 (2018)
  25. Kim M, "Immunoglobulin gene rearrangement in Koreans with multiple myeloma : clonality assessment and repertoire analysis using next-generation sequencing", PLoS One, 16, pp.e0253541~ (2021)
  26. Romano A, "Minimal residual disease assessment within the bone marrow of multiple myeloma : a review of caveats, clinical significance and future perspectives", Front Oncol, 9, pp.699~ (2019)
  27. Ng DP, "Flow cytometric myeloma measurable residual disease testing in the era of targeted therapies", Int J Lab Hematol, 43(S1), pp.71~77 (2021)
  28. Arcila ME, "Establishment of immunoglobulin heavy(IGH)chain clonality testing by next-generation sequencing for routine characterization of B-cell and plasma cell neoplasms", J Mol Diagn, 21, pp.330~342 (2019)
  29. Ho C, "Routine evaluation of minimal residual disease in myeloma using next-generation sequencing clonality testing : feasibility, challenges, and direct comparison with high-sensitivity flow cytometry", J Mol Diagn, 23, pp.181~199 (2021)
  30. Ha J, "Ig gene clonality analysis using next-generation sequencing for improved minimal residual disease detection with significant prognostic value in multiple myeloma patients", J Mol Diagn, 24, pp.48~56 (2022)
  31. Ho C, "Next-generation sequencing-based antigen-receptor gene clonality assays : will they become the clinical standard?", J Mol Diagn, 23, pp.1043~1046 (2021)
  32. Brüggemann M, "Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study", Leukemia, 33, pp.2241~2253 (2019)
  33. Cavo M, "Prognostic value of minimal residual disease negativity in myeloma : combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA", Blood, 139, pp.835~844 (2022)
  34. Martinez-Lopez J, "Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma", Blood, 123, pp.3073~3079 (2014)
  35. Avet-Loiseau H, "Minimal residual disease in multiple myeloma : final analysis of the IFM2009 trial", Blood, 130(S1), pp.435~ (2017)
  36. Yao Q, "Standardized minimal residual disease detection by next-generation sequencing in multiple myeloma", Front Oncol, 9, pp.449~ (2019)
  37. Rustad EH, "Baseline identification of clonal V(D)J sequences for DNA-based minimal residual disease detection in multiple myeloma", PLoS One, 14, pp.e0211600~ (2019)
  38. Medina A, "Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients", Blood Cancer J, 10, pp.14~ (2020)
  39. Medina A, "Comparison of next-generation sequencing(NGS)and next-generation flow(NGF)for minimal residual disease(MRD)assessment in multiple myeloma", Blood Cancer J, 10, pp.108~ (2020)
  40. Martinez-Lopez J, "Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma", Blood, 123, pp.3073~3079 (2014)
  41. Oliva S, "Multiparameter flow cytometry(MFC)and next generation sequencing(NGS)for minimal residual disease(MRD)evaluation : results of the FORTE trial in newly diagnosed multiple myeloma(MM)", J Clin Oncol, 38(S), pp.8533~ (2020)
  42. Avet-Loiseau H, "Concordance of post-consolidation minimal residual disease rates by multiparametric flow cytometry and next-generation sequencing in CASSIOPEIA", Clinical Lymphoma Myeloma and Leukemia, 19(S), pp.e3~e4 (2019)
  43. Cho H, "Real-world data on prognostic value of measurable residual disease assessment by fragment analysis or next-generation sequencing in multiple myeloma", Br J Haematol, 198, pp.503~514 (2022)
  44. Ferla V, "Minimal residual disease detection by next-generation sequencing in multiple myeloma : promise and challenges for response-adapted therapy", Front Oncol, 12, pp.932852~ (2022)
  45. Charalampous C, "Minimal residual disease assessment in multiple myeloma patients : minimal disease with maximal implications", Front Oncol, 11, pp.801851~ (2021)
  46. Garcés JJ, "Biological characterization and clinical relevance of circulating tumor cells : opening the Pandora's box of multiple myeloma", Cancers(Basel), 14, pp.1430~ (2022)
  47. Sanoja-Flores L, "Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells(CTPC)", Blood Cancer J, 8, pp.117~ (2018)
  48. Sanoja-Flores L, "Detection of circulating tumor plasma cells in monoclonal gammopathies : methods, pathogenic role, and clinical implications", Cancers(Basel), 12, pp.1499~ (2020)
  49. Gonsalves WI, "Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression", Leukemia, 31, pp.130~135 (2017)
  50. Periago A, "Circulating aberrant plasma cells allows risk stratification of patients with myeloma", Am J Hematol, 91, pp.E353~E355 (2016)

관련 논문AI추천

Clinical Utility of Next-Generation Flow-Based Minimal Residual Disease Assessment in Patients with Multiple Myeloma김기현, 김석진, 김선희, 김현영, 김희진, Cho Duck, Lim Dae Jin, Yoo In Young, Yoon Sang Eun대한진단검사의학회 · Annals of Laboratory Medicine2022 · 제42권 제5호Recent advances in multiple myeloma: a Korean perspectiveJae Hoon Lee, Junshik Hong대한내과학회 · The Korean Journal of Internal Medicine2016 · 제31권 제5호다발성골수종 환자의 진단 및 치료효과 추적을 위한 혈청 유리형 경쇄 정량검사의 의의김명신, 김용구, 민우성, 민창기, 임지향, 정선경, 한경자, 김명신1, 김용구1, 임지향1, 한경자1, 민우성2, 민창기2대한진단검사의학회 · Annals of Laboratory Medicine2008 · 제28권 제3호다발골수종 환자에서 자가조혈모세포이식 후에 관찰되는 올리고클론띠의 임상적 의의강혜진, 윤창은, 이진경, 장윤환, 홍석일, 홍영준대한진단검사의학회 · Laboratory Medicine Online2012 · 제2권 제1호다발골수종 환자의 염색체 이상과 예후관련 검사항목과의 연관성-단일 기관 연구이지원, 이진경, 장윤환, 홍석일, 홍영준대한진단검사의학회 · Annals of Laboratory Medicine2008 · 제28권 제6호백혈병 미세잔존질환 정량검출을 위한 실시간 역전사중합효소연쇄반응법의 유용성김다운, 김수현, 김인환, 김진각, 김형록, 김혜란, 나경아, 신명근, 정성두, 조정애, 천지선대한임상검사과학회 · 대한임상검사과학회지2009 · 제41권 제1호

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