IPSS-M clinical and genomic-based decision-making for HCT timing may improve outcomes in patients with MDS

May 2024

Researchers showed that the Molecular International Prognostic Scoring System (IPSS-M) changed the optimal timing of allogeneic hematopoietic cell transplant (alloHCT) for patients with myelodysplastic syndromes (MDS) when compared to the conventional Revised International Prognostic Scoring System (IPSS-R), resulting in a significant gain in life expectancy. Depending on risk category, some candidates for immediate transplant under IPSS-R would benefit from a delayed strategy using IPSS-M, and vice versa.

Adoption of IPSS-M by transplant providers enables more refined clinical and genomic-based decision-making and patient stratification, potentially improving alloHCT outcomes.

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AlloHCT is the only potentially curative treatment for patients with MDS. Providers must evaluate the benefits and risks of alloHCT for patients with MDS, as well as understand the optimal timing for HCT for a patient's specific MDS subtype.

Researchers aimed to develop and validate a decision support system to define the optimal timing of alloHCT for patients with MDS based on clinical and genomic information, as provided by the IPSS-M. A decision strategy was built to estimate the average survival over an 8-year time period (restricted mean survival time) for each combination of clinical and genomic predictors and to determine the optimal transplant policy by comparing different strategies.

This retrospective multi-center analysis examined a population of 7,118 patients across 26 institutions, stratified into training (n=4,627, 65%) and validation (n=2,491, 35%) cohorts balanced by age, sex, country (U.S. vs. EU), disease category and treatment (i.e., receiving alloHCT vs. not receiving alloHCT).

• Patients were ≥18 years old with a diagnosis of primary MDS (WHO 2016 criteria).
• Available information on IPSS-M–related variables was collected at diagnosis for patients who did not undergo alloHCT, before alloHCT for patients who were transplanted up front, and before starting disease-modifying treatments for patients who underwent pre-HCT cytoreduction.

Using IPSS-M, patients with either low and moderate-low risk benefited from delaying transplant, whereas for those belonging to moderately high-, high-, and very high-risk categories, immediate transplant was associated with a prolonged life expectancy.

Modeling decision analysis on IPSS-M versus conventional IPSS-R changed the transplant decision for a significant proportion of patients, resulting in a significant gain-in-life expectancy under an IPSS-M-based policy (p=0.001).

• 15% of candidates for immediate transplant under IPSS-R would benefit from a delayed strategy using IPSS-M.
• 19% of candidates for delayed transplant under IPSS-R would benefit from immediate alloHCT.

These results support the consideration of genomic features for the optimal timing of alloHCT, enabling enhanced decision-making that can significantly impact patient survival outcomes. Providers who adopt IPSS-M could better optimize transplant timing and identify patients who would benefit from immediate transplant.

IPSS-M could allow for more accurate patient stratification to evaluate treatment outcomes in future studies, which could improve the likelihood of treatment success for patients with MDS.

Hematology/oncology providers can enable optimal decision-making for alloHCT timing by referring patients with MDS for transplant consultation early. To support care coordination between referring providers and transplant centers, NMDP has developed consultation timing guidelines for major transplantable diseases, including MDS.

This figure compares optimal alloHCT timing under IPSS-R vs. IPSS-M.

Figure 3. Comparison of IPSS-R vs. IPSS-M transplant policy. (A) Whole MDS population potentially eligible for alloHCT (n=3,172); (B) Detailed description of change in transplant policy at the individual patient level, according to risk stratification by IPSS-M criteria.

Tentori CA, et al., published in J Clin Oncol