Therapeutic Outcomes and Prognostic Impact of Gene Mutations Including TP53 and SF3B1 in Patients with Del(5q) Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal hematopoietic stem cell neoplasms with several different subtypes. We retrospectively reviewed 132 patients with del(5q) MDS and described the treatment outcomes and prognostic impact of gene mutations. Lenalidomide was an effective treatment for patients with del(5q) MDS and many of them achieved at least hematologic improvement. Hypomethylating agents after lenalidomide failure did not show a survival advantage and outcomes in this setting were poor. There was no significant difference in overall survival (OS) comparing patients with or without TP53 mutations. Interestingly, those who harbored SF3B1 mutations have inferior survivals compared to wild-type. These findings may have management implications and should be externally validated in larger cohorts. Background: Genetic alterations are increasingly being recognized to play an important role in both diagnosis and prognosis of MDS. In general, MDS patients with SF3B1 mutations (MT) are known to have favorable outcomes whereas those with TP53 mutations have dismal survivals. However, it is unclear if the impact of these mutations applies to all subtypes of MDS including del(5q) which is known for its response to lenalidomide and better prognosis. Materials and Methods: We retrospectively reviewed 132 del(5q) MDS patients who were treated at the Moffitt Cancer Center (20012019). Results: Among patients who received lenalidomide (n = 98), 50%, 42.9%, and 7.1% achieved hematologic improvement or better, no response, and disease progression/death with a median overall survival (mOS) of 93.2, 72.4, and 25.6 months, respectively ( P < .0001). The mOS was 73.3 months but only 25.6 months after patients stopped lenalidomide. TP53 was the most common mutation accounting for 23.8% of the patients. Of the 63 patients with molecular data available, 23.8% harbored TP53 MT and 10% with SF3B1 MT. TP53 status did not impact OS (MT 86.4 vs. wild-type (WT) 73.3 months; P = .72) but those with SF3B1 mutations had a significantly shorter mOS compared to WT (23.9 vs. 83.5 months; P = .001). Multivariate analysis confirmed lenalidomide response and SF3B1 mutations are independently associated with outcomes. Conclusion: Our findings indicate many del(5q) MDS patients will benefit from lenalidomide but survival after its failure is limited. Mutations known to have prognostic impact in MDS at large may not have the same implications in the del(5q) subset.

Automated summary

This study retrospectively reviewed 132 del(5q) MDS patients and described the treatment outcomes and prognostic impact of gene mutations. The study found that lenalidomide was an effective treatment for del(5q) MDS patients, but hypomethylating agents after lenalidomide failure did not provide survival advantage. There was no significant difference in overall survival between patients with or without TP53 mutations, but patients with SF3B1 mutations had inferior survivals.