Researchers describe impact of SF3B1 mutations in myelodysplastic syndrome
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SF3B1 mutations occurred more frequently in de novo myelodysplastic syndromes than therapy-related myelodysplastic syndrome, according to results of a phase 2 study presented at Society of Hematologic Oncology Annual Meeting.
Additionally, SF3B1 mutations appeared associated with improved survival among patients with de novo vs. therapy-related myelodysplastic syndrome (MDS). However, among patients with treatment-related disease, those with SF3B1 mutations had better outcomes than those with wild-type SF3B1.
“When adjusted for comorbidities, those with therapy-related MDS still had significantly worse survival,” Virginia Volpe, MD, hematology and oncology fellow at H. Lee Moffitt Cancer Center & Research Institute, said during a presentation. “Complex cytogenetics, TP53 mutations and transformation to AML occurred more frequently with SF3B1 wild-type than SF3B1-mutated [disease]. To our knowledge, our data [are] the first to suggest that among therapy-related MDS, SF3B1 mutation may portend a better prognosis and [this subtype] behaves closer to de novo MDS with SF3B1 mutation.”
Acquired SF3B1 splicing mutation is the only somatic mutation generally associated with favorable outcomes among patients with MDS. It occurs in around 80% of patients with MDS and ring sideroblasts.
To better understand the clinical characteristics and outcomes associated with SF3B1 mutations, Volpe and colleagues analyzed 320 patients with MDS who harbored SF3B1 mutations. Of the patients, 289 had de novo MDS and 31 had therapy-related MDS.
Concomitant CBL mutations occurred less frequently in de novo MDS than therapy-related MDS (1% vs. 10%; P = .002). Otherwise, characteristics and concomitant mutations were similar between the groups.
Results showed that transformation to acute myeloid leukemia occurred at similar rates among patients with de novo and therapy-related MDS (12.5% vs. 12.9%).
However, patients with de novo MDS demonstrated significantly longer OS than patients with therapy-related MDS (103 months vs. 59 months; P = .001).
Researchers then analyzed a group of 272 patients with therapy-related MDS to compare outcomes between wild-type patients and those with the SF3B1 mutation (11%).
Complex cytogenetics occurred among 37.4% of the wild-type group compared with 10.3% of patients in the mutated group.
Researchers also observed concomitant TP53 mutations in 36.1% of patients with wild-type SF3B1 compared with 12.9% of patients with SF3B1 mutations.
Median OS was superior in those with SF3B1 mutations compared with patients with wild-type SF3B1 (43 months vs. 17 months; P = .004).
“In the future, we look to investigate the mortality rate among therapy-related MDS and why we have seen worse outcomes when adjusted for comorbidities,” Volpe said. “Long-term effects of prior treatments and age may play an important role. Additionally, the diagnosis of therapy-related MDS may benefit from a redefinition to not only include a clinical phenotype, but a molecular phenotype, as well.”
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Volpe V, et al. Abstract MDS-254. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting). Sept. 9-12, 2020.
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