Clinical Scorecard: STAG2 Mutation and Posttransplant Survival After Low-Intensity Induction in AML and Myelodysplastic Neoplasm/AML

At a Glance

Key Highlights

• Among 46 patients, six had STAG2 mutations; none died during a median follow-up of 34.7 months.
• Two-year overall survival was 100% for STAG2-mutated patients and 39.2% for STAG2 wild-type patients (p = 0.028).
• The post-HSCT relapse rate was 37.5% in STAG2 wild-type patients and 0% in STAG2-mutated patients (p = 0.16).
• Age category and DNMT3A mutation status were not associated with overall survival in this cohort; the three-factor score did not stratify survival (p = 0.42).
• The authors state that the small STAG2-mutated subgroup and limited venetoclax-free exposure prevent determining whether the association reflects venetoclax sensitivity or intrinsically more indolent disease.

Guideline-Based Recommendations

Diagnosis

• At diagnosis, mutational profiling was performed using a 54-myeloid-gene next-generation sequencing panel.

Management

• The study describes low-intensity induction followed by first allogeneic HSCT; induction regimens included low-dose cytarabine with or without venetoclax and hypomethylating agents with or without venetoclax.
• The article does not provide a treatment recommendation based on STAG2 status.

Monitoring & Follow-up

• Overall survival was measured from transplantation and estimated using the Kaplan–Meier method, with log-rank comparisons.
• The study also reported post-HSCT relapse rate and relapse-free survival by STAG2 status.

Risks

• The STAG2-mutated subgroup comprised six patients, limiting the precision and interpretation of the association.
• Only one STAG2-mutated patient received venetoclax-free therapy, so the cohort could not distinguish venetoclax sensitivity from intrinsically more indolent disease.
• The age and DNMT3A components of the previously reported score did not replicate as survival predictors in this cohort.

Patient & Prescribing Data

Retrospective cohort of 46 adults with newly diagnosed myelodysplastic neoplasm/AML or AML who received low-intensity induction and a first allogeneic transplant; median age was 63.5 years.

Induction was low-dose cytarabine plus venetoclax in 26 patients, low-dose cytarabine alone in 13, hypomethylating agent plus venetoclax in four, and hypomethylating agent alone in three. Five of six STAG2-mutated patients received venetoclax plus low-dose cytarabine.

Clinical Best Practices

• Interpret the reported STAG2 survival association in light of the small number of mutation-positive patients and the retrospective, single-center cohort.
• Do not assume that the age, DNMT3A, or composite-score associations from the index cohort were reproduced; they were not significant in this cohort.
• The authors identify cohorts with substantial venetoclax-free exposure as necessary to distinguish possible venetoclax sensitivity from intrinsically indolent disease.

Related Resources & Content

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