Spliceosome Mutations in MDS Have More Favorable Survival After Allogeneic HCT

Among patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) who undergo allogeneic hematopoietic cell transplantation (HCT), a retrospective study has found that spliceosome mutations were associated with more favorable survival outcomes than non-spliceosome mutations. The findings were published in Leukemia Research.

According to lead author Amrita Desai, MD, MPH, of City of Hope in Duarte, California, the need of the study was that “[t]he risks of allogeneic HCT should be balanced with its curative potential and therefore understanding the HCT outcomes of distinct MDS subsets is critical for appropriate timing of allogeneic HCT in suitable candidates.”

The study was conducted at a single center with a cohort of 258 patients where the median age was 66 years and 84.9 % of patients had MDS. Among the 126 patients who had molecular profiling, 45.2% had a spliceosome mutation. 78.6% of patients with spliceosome mutations and 73.7% of patients with non-spliceosome mutations received a reduced intensity conditioning (RIC) regimen.

For the total patient cohort, the non-relapse mortality (NRM) at 100 days of the study was 7.1%. At two years, overall survival was 66.5% and the cumulative incidence of relapse was 20.0%. The prevalence of Grade II–IV acute graft versus host disease (GVHD) at 100 days was 36.3% and of any chronic GVHD at two years was 48.4%.

Comparing outcomes at two years for patients with spliceosome mutations to those with non-spliceosome mutations, survival was greater among the former at 83.8% versus 55.9% (P=.002), as was progression-free survival at 73.7% versus 50.0% (P=.007). The cumulative incidence of relapse was 15.9% in patients with spliceosome mutations versus 18.5% in patients with non-spliceosome mutations (P=.59).

The investigators highlighted that at two years the NRM was significantly lower for patients with spliceosome mutations than for patients with non-spliceosome mutations, at 10.4% versus 31.5% (P=.009).

Dr. Desai noted that “[t]his favorable outcome of the spliceosome-mutated patients could have implications for timing of allogeneic HCT, particularly for patients in the intermediate MDS prognostic risk groups.”

The investigators found no difference in prevalence of acute or chronic GVHD among the patients by spliceosome versus non-spliceosome mutation type.

Reference

Desai A, Samara Y, Yang D, et al. Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation. Leuk Res. 2024;145:107565. doi:10.1016/j.leukres.2024.107565