MDS-2: A retrospective study of patients with Myelodysplastic Syndrome

Challenge

Myelodysplastic syndromes (MDS) are associated with cytogenetic abnormalities in almost 50% of de novo and 80% of therapy-related cases. Del(5q) is the most common karyotypic abnormality reported in 10–20% of de novo MDS. Lenalidomide is considered the standard of care treatment in such patients. Some studies have suggested the feasibility of discontinuing lenalidomide while still maintaing long-term response. However, robust conclusions are limited by the small numbers involved.

Impact

To demonstrate the impact of lenalidomide discontinuation on disease outcomes in del(5q) MDS patients.

To identify the variables associated with relapse on discontinuation of lenalidomide treatment in such patients.

To determine the optimal duration of lenalidomide treatment and explore the possibility of treatment discontinuation in selected patients.

Lenalidomide discontinuation could be cost saving for the National Health System, and also reduce toxicity and adverse events in patients, possibly resulting in a better quality of life.

Project Summary

The primary objective is to investigate the outcomes of patients with del(5q) MDS who discontinued lenalidomide treatment in terms of hematological response duration, cytogenetic response duration, disease progression and mortality. The secondary objective is to investigate biological markers of relapse after lenalidomide discontinuation. The eligibility criteria are: Age (≥18 years); MDS diagnosis according to 2008 or 2016 WHO classification; Cytogenetic abnormality in del(5q); Transfusion-dependent anemia before lenalidomide treatment; Red blood cell transfusion independence (RBC-TI) achieved with lenalidomide. Data will be collected from European participating centres through MDS national registers or specific datasets filled by each investigator. The current MDS data uploaded to the HARMONY Big Data Platform could also be incorporated into this study. The primary endpoint is: Event-free survival (EFS).

The secondary endpoints are: Overall survival (OS); Progression-free survival (PFS); RBC-TI; Time to acute myeloid leukemia; Response rate to lenalidomide re-challenge; Toxicities; Biological and clinical predictors of response duration after discontinuation; Cost-effectiveness analysis. This study will collect cytogenetic and molecular data from before and after lenalidomide discontinuation to find possible predictors of long-lasting response. These data will help deepen our knowledge on the biology of MDS with del(5q) and the effect of lenalidomide in clone selection or evolution. That could pave the way to build a more conclusive study on the optimal duration of lenalidomide treatment.

Ultimately, this retrospective study using the HARMONY Big Data Platform can provide much needed insight into the safety of lenalidomide and help further explore the possibility of treatment discontinuation in this selected group of patients harboring del(5q).

Public-private partnership for Big Data in Hematology

HARMONY and HARMONY PLUS are funded through the Innovative Medicines Initiative (IMI), Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. Funding is received from the IMI 2 Joint Undertaking and is listed under grant agreement for HARMONY No. 116026 and grant agreement for HARMONY PLUS No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA).