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

Platzbecker, Uwe; Fenaux, Pierre; Adès, Lionel; Giagounidis, Aristoteles; Santini, Valeria; Loosdrecht, Arjan A. van de; Bowen, David; Witte, Théo de; Garcia‐Manero, Guillermo; Hellström‐Lindberg, Eva; Germing, Ulrich; Stauder, Reinhard; Malcovati, Luca; Sekeres, Mikkael A.; Steensma, David P.; Gloaguen, Silke

doi:10.1182/blood-2018-06-857102

Cited by 112 publications

(133 citation statements)

References 27 publications

(35 reference statements)

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“…Responses to the HMAs were evaluated according to the International Working Group. [32][33][34] Patients who responded to treatment were defined as achieving a complete response (CR) or partial response (PR) in AML and CR or PR or hematologic improvement in MDS.…”

Section: Clinical Endpointsmentioning

confidence: 99%

Efficacy of posaconazole prophylaxis in acute myeloid leukemia and myelodysplastic syndrome patients treated with hypomethylating agents

Kang

Lee

Jeon

et al. 2020

Therapeutic Advances in Hematology

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Background: Although many acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients have been treated with hypomethylating agents (HMAs) as a substitute for intensive chemotherapy in recent years, the incidence of invasive fungal infections (IFIs) and the efficacy of posaconazole as antifungal prophylaxis in these patients are not well known to date. Methods: We retrospectively analyzed 280 AML and MDS patients treated with HMAs to identify IFI incidence and posaconazole efficacy as antifungal prophylaxis in these patients. Results: The overall incidence of probable or proven IFIs was 7.9% (22/280 patients): 11.5% in the no-use group (17/148 patients) and 3.8% in the posaconazole group (5/132 patients). Most IFIs occurred during the early cycles of the HMAs (median: 3 cycles; range: 1–8 cycles), especially in patients who had neutropenia or did not respond to HMAs. Posaconazole significantly lowered IFI incidence compared with that in the no-use group in univariate and multivariate analyses. Moreover, patients who had reduced liver function at HMA initiation, were treated with decitabine therapy, and did not respond to HMA chemotherapy were independently associated with a higher IFI risk. In subgroup analysis, posaconazole appeared to be more beneficial for patients with good Eastern Cooperative Oncology Group performance score or liver function at HMA initiation. Conclusion: Thus, in AML and MDS patients receiving HMAs, IFI risk may be high during the early cycles, especially when the underlying disease is not controlled. Posaconazole could represent antifungal prophylaxis in these patients; further studies are needed for its appropriate indications.

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Section: Clinical Endpointsmentioning

confidence: 99%

Efficacy of posaconazole prophylaxis in acute myeloid leukemia and myelodysplastic syndrome patients treated with hypomethylating agents

Kang

Lee

Jeon

et al. 2020

Therapeutic Advances in Hematology

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“…1). In addition, in the analysis that applied the new IWG 2018 response criteria, 33 a greater percentage of patients in the luspatercept group than in the placebo group had transfusion independence for 16 weeks or longer (19% vs. 4% during weeks 1 through 24, and 28% vs. 7% during weeks 1 through 48) ( Fig. 1).…”

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confidence: 99%

“…P values were determined with the use of a Cochran-Mantel-Haenszel test with stratification for average baseline red-cell transfusion burden (≥6 units per 8 weeks vs. <6 units per 8 weeks) and baseline Revised International Prognostic Scoring System score (very low or low risk vs. intermediate risk). An analysis that applied the new International Working Group 2018 response criteria33 with transfusion independence for 16 weeks or longer was also conducted.…”

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confidence: 99%

Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes

et al. 2020

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BACKGROUND Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study. METHODS In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. RESULTS Of the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspaterceptassociated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time. CONCLUSIONS Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesisstimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.)

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“…The term ‘safety’ in MDS‐COS is clearly related to its application under the perspective of clinical studies. The parameter ‘haematological improvement’ in MDS‐COS summarises the different aspects of haematological responses, whereas many more details – such as changes in different cell lines in peripheral blood, reduction of bone marrow blasts and transfusion need, and cytogenetic response – are given in the IWG measures, 4,5 as well as in a recent summary of erythroid response 28 . In general, the objectives of IWG response criteria are different from those of the MDS‐COS.…”

Section: Discussionmentioning

confidence: 99%

Development of a core outcome set for myelodysplastic syndromes – a Delphi study from the EUMDS Registry Group

et al. 2020

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Summary Treatment options for myelodysplastic syndromes (MDS) vary widely, depending on the natural disease course and patient‐related factors. Comparison of treatment effectiveness is challenging as different endpoints have been included in clinical trials and outcome reporting. Our goal was to develop the first MDS core outcome set (MDS‐COS) defining a minimum set of outcomes that should be reported in future clinical studies. We performed a comprehensive systematic literature review among MDS studies to extract patient‐ and/or clinically relevant outcomes. Clinical experts from the European LeukemiaNet MDS (EUMDS) identified 26 potential MDS core outcomes and participated in a three‐round Delphi survey. After the first survey (56 experts), 15 outcomes met the inclusion criteria and one additional outcome was included. The second round (38 experts) resulted in six included outcomes. In the third round, a final check on plausibility and practicality of the six included outcomes and their definitions was performed. The final MDS‐COS includes: health‐related quality of life, treatment‐related mortality, overall survival, performance status, safety, and haematological improvement. This newly developed MDS‐COS represents the first minimum set of outcomes aiming to enhance comparability across future MDS studies and facilitate a better understanding of treatment effectiveness.

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

Cited by 112 publications

References 27 publications

Efficacy of posaconazole prophylaxis in acute myeloid leukemia and myelodysplastic syndrome patients treated with hypomethylating agents

Efficacy of posaconazole prophylaxis in acute myeloid leukemia and myelodysplastic syndrome patients treated with hypomethylating agents

Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes

Development of a core outcome set for myelodysplastic syndromes – a Delphi study from the EUMDS Registry Group

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