icMDS recommendations for eligibility criteria based on risk and phase
| Eligibility criterion category . | Frontline . | Relapsed/refractory . | Additional comments . | |||
|---|---|---|---|---|---|---|
| LR-MDS early phase . | LR-MDS late phase . | HR-MDS early phase . | HR-MDS late phase . | |||
| Inclusion | ||||||
| Risk (IPSS, IPSS-R, IPSS-M) | X | X | X | X | X | Recommend for all trials |
| Assessment of disease classification by suitable hematopathological system | X | X | X | X | X | This can include WHO 2016, WHO 2022, or ICC 2022 based on clinical diagnosis at institution at which pathology is read out. To account for different classifications that may be used in different institutions, inclusion criteria should optimally be worded to allow cross-comparison between trials, that is, relying on a specific blast threshold and risk stratification rather than named MDS subgroups defined by 1 classification system. |
| Performance status/ECOG | X | X | X | X | X | Recommend for all trials |
| Blasts | X | X | X | X | X | Recommended for all trials because of the different definition of HR-MDS/AML in WHO or ICC classifications. Certain therapies may show signals in groups of patients with higher or lower blast counts. Specific end points may require blasts, for example, CR. |
| Hemoglobin | X | X | One pitfall is that this may limit inclusion of patients with symptomatic anemia who do not meet hemoglobin thresholds | |||
| RBC transfusion requirements | X | X | Consider in LR-MDS late-phase trials if early phase trials suggest preferential benefit in RBC transfusion–independent or –dependent patients. Decreasing RBC transfusion burden is more relevant in LR-MDS trials because disease progression is slower. Anemia and RBC transfusion dependency are the most frequent features affecting quality of life in LR-MDS. | |||
| Prior therapy | X | May inform sequencing of therapies in R/R setting. However, it may be more beneficial to state resolution from acute toxicities. Can consider if patients with less than one cycle (or other defined period) of prior therapy may still be considered “frontline.” | ||||
| Exclusion | ||||||
| LFTs | X | X | Appropriate in early-phase safety studies. Consider in late-phase studies if relevant to toxicity profile. Can consider additional cohort with more compromised LFTs in late-phase trials. If not biologically relevant and no safety signal, then overly restricts enrollment. | |||
| Renal function, MDRD or CKD-EPI | X | X | Appropriate in early-phase safety studies. Consider in late-phase trials if relevant to toxicity profile. Can consider additional cohort with more compromised renal function in late-phase trials. If not biologically relevant and no safety signal, then overly restricts enrollment. | |||
| NYHA class | X | X | Consider in late-phase trials if relevant to toxicity profile. If no safety signal present in early-phase trials, NYHA class may remain stable and not be affected by in late-phase studies. | |||
| QTc | X | X | Recommend use of well-characterized QT correction such as the Fridericia or Framingham formulas.27 Appropriate in early-phase safety studies or studies requiring use of concomitant medications that prolong the QTc. Consider in late-phase trials if relevant to toxicity profile. If no safety signal, then overly restricts enrollment. | |||
| Uncontrolled infection | X | X | X | X | X | Recommend for all trials |
| Chronic viral illnesses | X | X | Therapy may increase risk of viral reactivation and appropriate in early-phase trials. Consider in late-phase trials if relevant to toxicity profile. Specific ART drugs may have overlapping toxicities, and therapy may increase risk of opportunistic infection. | |||
| Washout periods | X | Improves attribution of effect to investigational therapy. One pitfall is that HR-MDS may require more immediate therapy initiation within the washout period. Additionally, half-lives may not be known for investigational agents. | ||||
| Eligibility criterion category . | Frontline . | Relapsed/refractory . | Additional comments . | |||
|---|---|---|---|---|---|---|
| LR-MDS early phase . | LR-MDS late phase . | HR-MDS early phase . | HR-MDS late phase . | |||
| Inclusion | ||||||
| Risk (IPSS, IPSS-R, IPSS-M) | X | X | X | X | X | Recommend for all trials |
| Assessment of disease classification by suitable hematopathological system | X | X | X | X | X | This can include WHO 2016, WHO 2022, or ICC 2022 based on clinical diagnosis at institution at which pathology is read out. To account for different classifications that may be used in different institutions, inclusion criteria should optimally be worded to allow cross-comparison between trials, that is, relying on a specific blast threshold and risk stratification rather than named MDS subgroups defined by 1 classification system. |
| Performance status/ECOG | X | X | X | X | X | Recommend for all trials |
| Blasts | X | X | X | X | X | Recommended for all trials because of the different definition of HR-MDS/AML in WHO or ICC classifications. Certain therapies may show signals in groups of patients with higher or lower blast counts. Specific end points may require blasts, for example, CR. |
| Hemoglobin | X | X | One pitfall is that this may limit inclusion of patients with symptomatic anemia who do not meet hemoglobin thresholds | |||
| RBC transfusion requirements | X | X | Consider in LR-MDS late-phase trials if early phase trials suggest preferential benefit in RBC transfusion–independent or –dependent patients. Decreasing RBC transfusion burden is more relevant in LR-MDS trials because disease progression is slower. Anemia and RBC transfusion dependency are the most frequent features affecting quality of life in LR-MDS. | |||
| Prior therapy | X | May inform sequencing of therapies in R/R setting. However, it may be more beneficial to state resolution from acute toxicities. Can consider if patients with less than one cycle (or other defined period) of prior therapy may still be considered “frontline.” | ||||
| Exclusion | ||||||
| LFTs | X | X | Appropriate in early-phase safety studies. Consider in late-phase studies if relevant to toxicity profile. Can consider additional cohort with more compromised LFTs in late-phase trials. If not biologically relevant and no safety signal, then overly restricts enrollment. | |||
| Renal function, MDRD or CKD-EPI | X | X | Appropriate in early-phase safety studies. Consider in late-phase trials if relevant to toxicity profile. Can consider additional cohort with more compromised renal function in late-phase trials. If not biologically relevant and no safety signal, then overly restricts enrollment. | |||
| NYHA class | X | X | Consider in late-phase trials if relevant to toxicity profile. If no safety signal present in early-phase trials, NYHA class may remain stable and not be affected by in late-phase studies. | |||
| QTc | X | X | Recommend use of well-characterized QT correction such as the Fridericia or Framingham formulas.27 Appropriate in early-phase safety studies or studies requiring use of concomitant medications that prolong the QTc. Consider in late-phase trials if relevant to toxicity profile. If no safety signal, then overly restricts enrollment. | |||
| Uncontrolled infection | X | X | X | X | X | Recommend for all trials |
| Chronic viral illnesses | X | X | Therapy may increase risk of viral reactivation and appropriate in early-phase trials. Consider in late-phase trials if relevant to toxicity profile. Specific ART drugs may have overlapping toxicities, and therapy may increase risk of opportunistic infection. | |||
| Washout periods | X | Improves attribution of effect to investigational therapy. One pitfall is that HR-MDS may require more immediate therapy initiation within the washout period. Additionally, half-lives may not be known for investigational agents. | ||||
X indicates recommended clarification with inclusion or exclusion criteria. ART, antiretroviral therapy; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CR, complete remission; ECOG, Eastern Oncology Cooperative Group; ICC, International Consensus Classification; IPSS-R, revised IPSS; LFT, liver function test; MDRD, Modification of Diet in Renal Disease; NYHA, New York Heart Association; R/R, relapsed/refractory; RBC, red blood cell; WHO, World Health Organization.