Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

U. Platzbecker, P. Fenaux, L. Adès, A. Giagounidis, V. Santini, A.A. Van De Loosdrecht, D. Bowen, T. De Witte, G. Garcia-Manero, E. Hellström-Lindberg, U. Germing, R. Stauder, L. Malcovati, M.A. Sekeres, D.P. Steensma, S. Gloaguen

Research output: Contribution to journalArticle

Abstract

The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups. © 2019 by The American Society of Hematology
Original languageEnglish
Pages (from-to)1020-1030
Number of pages11
JournalBlood
Volume133
Issue number10
DOIs
Publication statusPublished - 2019

Fingerprint

Myelodysplastic Syndromes
Clinical Trials
Therapeutics

Keywords

  • hemoglobin
  • Article
  • blood cell count
  • blood transfusion
  • hemoglobin determination
  • human
  • myelodysplastic syndrome
  • neutrophil
  • practice guideline
  • priority journal
  • thrombocyte

Cite this

Platzbecker, U., Fenaux, P., Adès, L., Giagounidis, A., Santini, V., Van De Loosdrecht, A. A., ... Gloaguen, S. (2019). Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials. Blood, 133(10), 1020-1030. https://doi.org/10.1182/blood-2018-06-857102

Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials. / Platzbecker, U.; Fenaux, P.; Adès, L.; Giagounidis, A.; Santini, V.; Van De Loosdrecht, A.A.; Bowen, D.; De Witte, T.; Garcia-Manero, G.; Hellström-Lindberg, E.; Germing, U.; Stauder, R.; Malcovati, L.; Sekeres, M.A.; Steensma, D.P.; Gloaguen, S.

In: Blood, Vol. 133, No. 10, 2019, p. 1020-1030.

Research output: Contribution to journalArticle

Platzbecker, U, Fenaux, P, Adès, L, Giagounidis, A, Santini, V, Van De Loosdrecht, AA, Bowen, D, De Witte, T, Garcia-Manero, G, Hellström-Lindberg, E, Germing, U, Stauder, R, Malcovati, L, Sekeres, MA, Steensma, DP & Gloaguen, S 2019, 'Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials', Blood, vol. 133, no. 10, pp. 1020-1030. https://doi.org/10.1182/blood-2018-06-857102
Platzbecker U, Fenaux P, Adès L, Giagounidis A, Santini V, Van De Loosdrecht AA et al. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials. Blood. 2019;133(10):1020-1030. https://doi.org/10.1182/blood-2018-06-857102
Platzbecker, U. ; Fenaux, P. ; Adès, L. ; Giagounidis, A. ; Santini, V. ; Van De Loosdrecht, A.A. ; Bowen, D. ; De Witte, T. ; Garcia-Manero, G. ; Hellström-Lindberg, E. ; Germing, U. ; Stauder, R. ; Malcovati, L. ; Sekeres, M.A. ; Steensma, D.P. ; Gloaguen, S. / Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials. In: Blood. 2019 ; Vol. 133, No. 10. pp. 1020-1030.
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title = "Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials",
abstract = "The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups. {\circledC} 2019 by The American Society of Hematology",
keywords = "hemoglobin, Article, blood cell count, blood transfusion, hemoglobin determination, human, myelodysplastic syndrome, neutrophil, practice guideline, priority journal, thrombocyte",
author = "U. Platzbecker and P. Fenaux and L. Ad{\`e}s and A. Giagounidis and V. Santini and {Van De Loosdrecht}, A.A. and D. Bowen and {De Witte}, T. and G. Garcia-Manero and E. Hellstr{\"o}m-Lindberg and U. Germing and R. Stauder and L. Malcovati and M.A. Sekeres and D.P. Steensma and S. Gloaguen",
note = "Cited By :2 Export Date: 10 October 2019 CODEN: BLOOA Correspondence Address: Platzbecker, U.; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig, Johannisallee 32 A, Germany; email: uwe.platzbecker@medizin.uni-leipzig.de Chemicals/CAS: hemoglobin, 9008-02-0 Funding details: Council of Science and Technology, U.P. Funding details: Celgene Funding text 1: Conflict-of-interest disclosure: U.P. and P.F. have received renumeration and research funding from Celgene Corporation. The remaining authors declare no competing financial interests. References: Balducci, L., Transfusion independence in patients with myelodysplastic syndromes: Impact on outcomes and quality of life (2006) Cancer, 106 (10), pp. 2087-2094; Alessandrino, E.P., Amadori, S., Barosi, G., Evidence- And consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology (2002) Haematologica, 87 (12), pp. 1286-1306. , Italian Society of Hematology; Greenberg, P.L., Current therapeutic approaches for patients with myelodysplastic syndromes (2010) Br J Haematol, 150 (2), pp. 131-143; Heptinstall, K., Quality of life (QoL) in myelodysplastic syndromes (MDS): An update of results from US & European patient forums (2007) Leuk Res, 31, p. 107; Platzbecker, U., Hofbauer, L.C., Ehninger, G., H{\"o}lig, K., The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes (2012) Leuk Res, 36 (5), pp. 525-536; Cheson, B.D., Bennett, J.M., Kantarjian, H., Report of an international working group to standardize response criteria for myelodysplastic syndromes (2000) Blood, 96 (12), pp. 3671-3674; Cheson, B.D., Greenberg, P.L., Bennett, J.M., Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia (2006) Blood, 108 (2), pp. 419-425; Santini, V., Almeida, A., Giagounidis, A., Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents (2016) J Clin Oncol, 34 (25), pp. 2988-2996; Platzbecker, U., Symeonidis, A., Oliva, E.N., A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes (2017) Leukemia, 31 (9), pp. 1944-1950; Fenaux, P., Santini, V., Spiriti, M.A.A., A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-a in anemic patients with low-risk MDS Leukemia, , published online ahead of print 30 March 2018; Bryant, A.L., Drier, S.W., Lee, S., Bennett, A.V., A systematic review of patient reported outcomes in phase II or III clinical trials of myelodysplastic syndromes and acute myeloid leukemia (2018) Leuk Res, 70, pp. 106-116; Crawford, J., Cella, D., Cleeland, C.S., Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy (2002) Cancer, 95 (4), pp. 888-895; Dharmarajan, T.S., Pankratov, A., Morris, E., Anemia: Its impact on hospitalizations and length of hospital stay in nursing home and community older adults (2008) J Am Med Dir Assoc, 9 (5), pp. 354-359; Dharmarajan, T.S., Avula, S., Norkus, E.P., Anemia increases risk for falls in hospitalized older adults: An evaluation of falls in 362 hospitalized, ambulatory, long-term care, and community patients (2006) J Am Med Dir Assoc, 7 (5), pp. 287-293; Stauder, R., Yu, G., Koinig, K.A., Health-related quality of life in lower-risk MDS patients compared with age- And sex-matched reference populations: A European LeukemiaNet study (2018) Leukemia, 32 (6), pp. 1380-1392; Kao, J.M., McMillan, A., Greenberg, P.L., International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: Impact of cytopenias on clinical outcomes in myelodysplastic syndromes (2008) Am J Hematol, 83 (10), pp. 765-770; Jansen, A.J., Essink-Bot, M.L., Beckers, E.A., Hop, W.C., Schipperus, M.R., Van Rhenen, D.J., Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes (2003) Br J Haematol, 121 (2), pp. 270-274; Caocci, G., Baccoli, R., Ledda, A., Littera, R., La Nasa, G., A mathematical model for the evaluation of amplitude of hemoglobin fluctuations in elderly anemic patients affected by myelodysplastic syndromes: Correlation with quality of life and fatigue (2007) Leuk Res, 31 (2), pp. 249-252; Oliva, E.N., Finelli, C., Santini, V., Quality of life and physicians’ perception in myelodysplastic syndromes (2012) Am J Blood Res, 2 (2), pp. 136-147; Efficace, F., Gaidano, G., Breccia, M., Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes (2015) Br J Haematol, 168 (3), pp. 361-370; Steensma, D.P., Heptinstall, K.V., Johnson, V.M., Common troublesome symptoms and their impact on quality of life in patients with myelodysplastic syndromes (MDS): Results of a large internet-based survey (2008) Leuk Res, 32 (5), pp. 691-698; Malcovati, L., Hellstr{\"o}m-Lindberg, E., Bowen, D., Diagnosis and treatment of primary myelodysplastic syndromes in adults: Recommendations from the European Leukemianet (2013) Blood, 122 (17), pp. 2943-2964. , European LeukemiaNet; Santini, V., Almeida, A., Giagounidis, A., Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents (2016) J Clin Oncol, 34 (25), pp. 2988-2996; Raza, A., Reeves, J.A., Feldman, E.J., Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q (2008) Blood, 111 (1), pp. 86-93; Toma, A., Kosmider, O., Chevret, S., Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion (2016) Leukemia, 30 (4), pp. 897-905; Hellstr{\"o}m-Lindberg, E., Gulbrandsen, N., Lindberg, G., A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin 1 granulocyte colony-stimulating factor: Significant effects on quality of life (2003) Br J Haematol, 120 (6), pp. 1037-1046; Greenberg, P.L., Tuechler, H., Schanz, J., Revised International Prognostic Scoring System for myelodysplastic syndromes (2012) Blood, 120 (12), pp. 2454-2465; Gaweda, A.E., Nathanson, B.H., Jacobs, A.A., Aronoff, G.R., Germain, M.J., Brier, M.E., Determining optimum hemoglobin sampling for anemia management from every-treatment data (2010) Clin J Am Soc Nephrol, 5 (11), pp. 1939-1945; Fishbane, S., Besarab, A., Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets (2007) Clin J Am Soc Nephrol, 2 (6), pp. 1274-1282; Efficace, F., Cottone, F., Abel, G., Patient-reported outcomes enhance the survival prediction of traditional disease risk classifications: An international study in patients with myelodysplastic syndromes (2018) Cancer, 124 (6), pp. 1251-1259",
year = "2019",
doi = "10.1182/blood-2018-06-857102",
language = "English",
volume = "133",
pages = "1020--1030",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

AU - Platzbecker, U.

AU - Fenaux, P.

AU - Adès, L.

AU - Giagounidis, A.

AU - Santini, V.

AU - Van De Loosdrecht, A.A.

AU - Bowen, D.

AU - De Witte, T.

AU - Garcia-Manero, G.

AU - Hellström-Lindberg, E.

AU - Germing, U.

AU - Stauder, R.

AU - Malcovati, L.

AU - Sekeres, M.A.

AU - Steensma, D.P.

AU - Gloaguen, S.

N1 - Cited By :2 Export Date: 10 October 2019 CODEN: BLOOA Correspondence Address: Platzbecker, U.; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig, Johannisallee 32 A, Germany; email: uwe.platzbecker@medizin.uni-leipzig.de Chemicals/CAS: hemoglobin, 9008-02-0 Funding details: Council of Science and Technology, U.P. Funding details: Celgene Funding text 1: Conflict-of-interest disclosure: U.P. and P.F. have received renumeration and research funding from Celgene Corporation. The remaining authors declare no competing financial interests. References: Balducci, L., Transfusion independence in patients with myelodysplastic syndromes: Impact on outcomes and quality of life (2006) Cancer, 106 (10), pp. 2087-2094; Alessandrino, E.P., Amadori, S., Barosi, G., Evidence- And consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology (2002) Haematologica, 87 (12), pp. 1286-1306. , Italian Society of Hematology; Greenberg, P.L., Current therapeutic approaches for patients with myelodysplastic syndromes (2010) Br J Haematol, 150 (2), pp. 131-143; Heptinstall, K., Quality of life (QoL) in myelodysplastic syndromes (MDS): An update of results from US & European patient forums (2007) Leuk Res, 31, p. 107; Platzbecker, U., Hofbauer, L.C., Ehninger, G., Hölig, K., The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes (2012) Leuk Res, 36 (5), pp. 525-536; Cheson, B.D., Bennett, J.M., Kantarjian, H., Report of an international working group to standardize response criteria for myelodysplastic syndromes (2000) Blood, 96 (12), pp. 3671-3674; Cheson, B.D., Greenberg, P.L., Bennett, J.M., Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia (2006) Blood, 108 (2), pp. 419-425; Santini, V., Almeida, A., Giagounidis, A., Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents (2016) J Clin Oncol, 34 (25), pp. 2988-2996; Platzbecker, U., Symeonidis, A., Oliva, E.N., A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes (2017) Leukemia, 31 (9), pp. 1944-1950; Fenaux, P., Santini, V., Spiriti, M.A.A., A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-a in anemic patients with low-risk MDS Leukemia, , published online ahead of print 30 March 2018; Bryant, A.L., Drier, S.W., Lee, S., Bennett, A.V., A systematic review of patient reported outcomes in phase II or III clinical trials of myelodysplastic syndromes and acute myeloid leukemia (2018) Leuk Res, 70, pp. 106-116; Crawford, J., Cella, D., Cleeland, C.S., Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy (2002) Cancer, 95 (4), pp. 888-895; Dharmarajan, T.S., Pankratov, A., Morris, E., Anemia: Its impact on hospitalizations and length of hospital stay in nursing home and community older adults (2008) J Am Med Dir Assoc, 9 (5), pp. 354-359; Dharmarajan, T.S., Avula, S., Norkus, E.P., Anemia increases risk for falls in hospitalized older adults: An evaluation of falls in 362 hospitalized, ambulatory, long-term care, and community patients (2006) J Am Med Dir Assoc, 7 (5), pp. 287-293; Stauder, R., Yu, G., Koinig, K.A., Health-related quality of life in lower-risk MDS patients compared with age- And sex-matched reference populations: A European LeukemiaNet study (2018) Leukemia, 32 (6), pp. 1380-1392; Kao, J.M., McMillan, A., Greenberg, P.L., International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: Impact of cytopenias on clinical outcomes in myelodysplastic syndromes (2008) Am J Hematol, 83 (10), pp. 765-770; Jansen, A.J., Essink-Bot, M.L., Beckers, E.A., Hop, W.C., Schipperus, M.R., Van Rhenen, D.J., Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes (2003) Br J Haematol, 121 (2), pp. 270-274; Caocci, G., Baccoli, R., Ledda, A., Littera, R., La Nasa, G., A mathematical model for the evaluation of amplitude of hemoglobin fluctuations in elderly anemic patients affected by myelodysplastic syndromes: Correlation with quality of life and fatigue (2007) Leuk Res, 31 (2), pp. 249-252; Oliva, E.N., Finelli, C., Santini, V., Quality of life and physicians’ perception in myelodysplastic syndromes (2012) Am J Blood Res, 2 (2), pp. 136-147; Efficace, F., Gaidano, G., Breccia, M., Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes (2015) Br J Haematol, 168 (3), pp. 361-370; Steensma, D.P., Heptinstall, K.V., Johnson, V.M., Common troublesome symptoms and their impact on quality of life in patients with myelodysplastic syndromes (MDS): Results of a large internet-based survey (2008) Leuk Res, 32 (5), pp. 691-698; Malcovati, L., Hellström-Lindberg, E., Bowen, D., Diagnosis and treatment of primary myelodysplastic syndromes in adults: Recommendations from the European Leukemianet (2013) Blood, 122 (17), pp. 2943-2964. , European LeukemiaNet; Santini, V., Almeida, A., Giagounidis, A., Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents (2016) J Clin Oncol, 34 (25), pp. 2988-2996; Raza, A., Reeves, J.A., Feldman, E.J., Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q (2008) Blood, 111 (1), pp. 86-93; Toma, A., Kosmider, O., Chevret, S., Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion (2016) Leukemia, 30 (4), pp. 897-905; Hellström-Lindberg, E., Gulbrandsen, N., Lindberg, G., A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin 1 granulocyte colony-stimulating factor: Significant effects on quality of life (2003) Br J Haematol, 120 (6), pp. 1037-1046; Greenberg, P.L., Tuechler, H., Schanz, J., Revised International Prognostic Scoring System for myelodysplastic syndromes (2012) Blood, 120 (12), pp. 2454-2465; Gaweda, A.E., Nathanson, B.H., Jacobs, A.A., Aronoff, G.R., Germain, M.J., Brier, M.E., Determining optimum hemoglobin sampling for anemia management from every-treatment data (2010) Clin J Am Soc Nephrol, 5 (11), pp. 1939-1945; Fishbane, S., Besarab, A., Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets (2007) Clin J Am Soc Nephrol, 2 (6), pp. 1274-1282; Efficace, F., Cottone, F., Abel, G., Patient-reported outcomes enhance the survival prediction of traditional disease risk classifications: An international study in patients with myelodysplastic syndromes (2018) Cancer, 124 (6), pp. 1251-1259

PY - 2019

Y1 - 2019

N2 - The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups. © 2019 by The American Society of Hematology

AB - The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups. © 2019 by The American Society of Hematology

KW - hemoglobin

KW - Article

KW - blood cell count

KW - blood transfusion

KW - hemoglobin determination

KW - human

KW - myelodysplastic syndrome

KW - neutrophil

KW - practice guideline

KW - priority journal

KW - thrombocyte

U2 - 10.1182/blood-2018-06-857102

DO - 10.1182/blood-2018-06-857102

M3 - Article

VL - 133

SP - 1020

EP - 1030

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -