Summary of key considerations by clinical trial focus topic
| Focus . | Key considerations . |
|---|---|
| Risk stratification and eligibility | When designing a trial, classification system (ICC or WHO5) should be selected to clearly define the population being studied |
| Sufficient information should be collected to allow for retrospective classification using either ICC or WHO5 | |
| Either IPSS-R or IPSS-M should be used to clearly risk stratify the target population being studied | |
| Sufficient information should be collected to allow for retrospective prognostication using either IPSS-R or IPSS-M | |
| Minimize exclusions and barriers to protocol eligibility | |
| Response criteria | Collection of responses per IWG 2023 response criteria in addition to earlier response criteria will facilitate prospective validation |
| In HR-MDS, CR + PR with durability remains a clinically meaningful end point that should be supported by improvements in OS | |
| In LR-MDS, collect data on HI-E per IWG 2018 criteria will allow for prospective validation | |
| Time-to-event end points | Time-to-event end points should be specific to MDS population; eg, disease risk |
| In HR-MDS, OS remains the gold-standard time-to-event end point | |
| EFS and PFS may be considered as time-to-event end points but require prospective validation | |
| In LR-MDS, transfusion-free survival is a potential end point that requires a standard definition and prospective validation | |
| OS is an important efficacy and safety end point to include in all MDS trials | |
| Transfusion end points | A standard hemoglobin transfusion threshold of 7.5 to 8 g/dL can be considered for most patients |
| Transfusion density assessed over 16 weeks before enrollment allows for the definition of low or high burden | |
| 16+ week TI should be considered clinically meaningful | |
| Primary analysis should be based on all transfusions in ITT population followed by sensitivity analyses considering causality of transfusions | |
| Consider a "time without transfusion reliance" type of analysis | |
| Functional assessments and clinical trial integration | A prespecified, comprehensive assessment of PRO end points should be included in all MDS clinical trials |
| Baseline data on comorbidities, symptoms, disability, and physical functioning should be collected using well-defined and reliable tools | |
| Consider using PRFs in clinical trial design (eg, for stratification factors and eligibility criteria) | |
| Biomarker and MRD assays and development | Evaluate both NGS and flow cytometry for MRD detection and store DNA samples for future analysis |
| Common disease response criteria (ie, CR per IWG 2023) and clear thresholds for MRD response are needed to interpret MRD data and ensure consistency across trials | |
| Standardize assay development and define the optimal sensitivity and specificity of analyte measurements | |
| Consider documentation of MRD results quantitatively over the treatment course, particularly in patients with HR-MDS | |
| Collect biomarkers specific to different therapeutic or clinical contexts (ie, therapies targeting inflammatory pathways, methylation, or a specific targeted mutation) |
| Focus . | Key considerations . |
|---|---|
| Risk stratification and eligibility | When designing a trial, classification system (ICC or WHO5) should be selected to clearly define the population being studied |
| Sufficient information should be collected to allow for retrospective classification using either ICC or WHO5 | |
| Either IPSS-R or IPSS-M should be used to clearly risk stratify the target population being studied | |
| Sufficient information should be collected to allow for retrospective prognostication using either IPSS-R or IPSS-M | |
| Minimize exclusions and barriers to protocol eligibility | |
| Response criteria | Collection of responses per IWG 2023 response criteria in addition to earlier response criteria will facilitate prospective validation |
| In HR-MDS, CR + PR with durability remains a clinically meaningful end point that should be supported by improvements in OS | |
| In LR-MDS, collect data on HI-E per IWG 2018 criteria will allow for prospective validation | |
| Time-to-event end points | Time-to-event end points should be specific to MDS population; eg, disease risk |
| In HR-MDS, OS remains the gold-standard time-to-event end point | |
| EFS and PFS may be considered as time-to-event end points but require prospective validation | |
| In LR-MDS, transfusion-free survival is a potential end point that requires a standard definition and prospective validation | |
| OS is an important efficacy and safety end point to include in all MDS trials | |
| Transfusion end points | A standard hemoglobin transfusion threshold of 7.5 to 8 g/dL can be considered for most patients |
| Transfusion density assessed over 16 weeks before enrollment allows for the definition of low or high burden | |
| 16+ week TI should be considered clinically meaningful | |
| Primary analysis should be based on all transfusions in ITT population followed by sensitivity analyses considering causality of transfusions | |
| Consider a "time without transfusion reliance" type of analysis | |
| Functional assessments and clinical trial integration | A prespecified, comprehensive assessment of PRO end points should be included in all MDS clinical trials |
| Baseline data on comorbidities, symptoms, disability, and physical functioning should be collected using well-defined and reliable tools | |
| Consider using PRFs in clinical trial design (eg, for stratification factors and eligibility criteria) | |
| Biomarker and MRD assays and development | Evaluate both NGS and flow cytometry for MRD detection and store DNA samples for future analysis |
| Common disease response criteria (ie, CR per IWG 2023) and clear thresholds for MRD response are needed to interpret MRD data and ensure consistency across trials | |
| Standardize assay development and define the optimal sensitivity and specificity of analyte measurements | |
| Consider documentation of MRD results quantitatively over the treatment course, particularly in patients with HR-MDS | |
| Collect biomarkers specific to different therapeutic or clinical contexts (ie, therapies targeting inflammatory pathways, methylation, or a specific targeted mutation) |
HI-E, Hematologic improvement-erythroid; ITT, intention-to-treat.