What is the prognosis of Myelodysplastic Syndromes (MDS) with 5q deletion?

From the Guidelines

The prognosis for Myelodysplastic Syndromes (MDS) with 5q deletion is generally favorable, with approximately 50% of patients achieving transfusion independence and 23%–57% showing cytogenetic response with lenalidomide treatment, as reported in a 2019 study published in the Journal of Internal Medicine 1.

Key Considerations

• The presence of a TP53 mutation or marrow progenitors with strong p53 staining is associated with an increased risk of progression to acute myeloid leukemia (AML) 1.
• Lenalidomide is approved in Europe for the treatment of lower-risk MDS patients with del(5q) who have not responded to treatment with erythropoietin-stimulating agents, with a duration of response of approximately 2 years 1.
• The Nordic MDS and chronic myelomonocytic leukaemia (CMML) care programme recommends evaluating lower-risk del(5q) patients with TP53 mutation detected by deep sequencing or the presence of >2% marrow cells with strong p53 staining for treatment other than lenalidomide 1.

Treatment and Management

• Lenalidomide is the standard treatment for MDS with 5q deletion, with about 50% of patients achieving transfusion independence and 23%–57% showing cytogenetic response 1.
• Treatment should continue as long as it remains effective and tolerable, with regular monitoring of blood counts to manage potential side effects such as neutropenia and thrombocytopenia.
• Alternative options for patients who don't respond to lenalidomide or lose response include hypomethylating agents (azacitidine or decitabine), supportive care with transfusions, or consideration for allogeneic stem cell transplantation in eligible patients.

From the Research

Prognosis of Myelodysplastic Syndromes (MDS) with 5q Deletion

The prognosis of MDS with 5q deletion is generally favorable, especially when the deletion is isolated 2, 3, 4. Key factors that influence the prognosis include:

• The presence of additional chromosomal abnormalities
• The percentage of blasts in the bone marrow
• Transfusion dependence

Factors Influencing Prognosis

• Isolated del(5q) is associated with a favorable risk profile and can be treated with lenalidomide 4
• The presence of additional cytogenetic abnormalities can turn MDS with del(5q) into high-risk forms of MDS 4
• Patients with del(5q) and <10% blasts have a median survival of 12 months, but this can range from 6-33 months depending on the presence of additional abnormalities 5

Treatment and Response

• Lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS, leading to complete cytogenetic and molecular responses in some cases 2, 6, 3
• The mechanism of action of lenalidomide is thought to involve targeting aberrant signaling pathways caused by haplosufficiency of specific genes in the commonly deleted region on chromosome 5 2
• Treatment with lenalidomide can lead to durable responses, with some patients remaining in hematological response for long periods of time even after discontinuation of treatment 6

Outcome and Survival

• The median survival for patients with MDS and deletion 5q is 9 months, but this can vary depending on the presence of additional abnormalities 5
• Patients with isolated del(5q) have a median survival of 33 months, while those with del(5q) and additional abnormalities have a poorer prognosis 5