6579 Background: Although tyrosine kinase inhibitors (TKIs) have markedly improved outcomes in chronic myeloid leukemia (CML), transformation to acute myeloid leukemia (AML) remains a devastating event with poor prognosis. Intensive induction chemotherapy with cytarabine and anthracycline (7+3) is standard, but many patients are older or frail and unable to tolerate intensive therapy. Azacitidine plus venetoclax (aza-ven) has emerged as a low-intensity alternative; however, real-world comparative outcome data in CML-transformed AML remain limited. We conducted a large real-world analysis to compare survival and early clinical outcomes with 7+3 versus aza-ven. Methods: Adult patients with CML transformed to AML who received induction therapy between January 1, 2010, and June 1, 2025, were identified using the TriNetX Research Network. Patients were classified by receipt of 7+3 or azacitidine plus venetoclax within one year before or after allogeneic hematopoietic stem cell transplantation. Overall survival (OS) was evaluated using Kaplan–Meier analysis with hazard ratios (HRs) and log-rank testing. Early clinical outcomes were compared using z-tests with risk differences (RD), risk ratios (RR), and 95% confidence intervals (CI). Results: A total of 280 patients were included, of whom 222 received 7+3 and 58 received azacitidine plus venetoclax (aza-ven). Patients treated with aza-ven had a higher comorbidity burden and lower baseline albumin, consistent with a frailer population. Early infectious complications within 30 days occurred in 53.2% of patients receiving 7+3 and 58.6% receiving aza-ven (risk difference RD −5.47%, 95% CI −19.74% to 8.81%; risk ratio RR 0.91, 95% CI 0.71–1.16; p=0.46). One-year overall survival was similar between groups (66.2% vs 68.1%; hazard ratio HR 1.03, 95% CI 0.62–1.72; log-rank p=0.91). Hospitalization within 30 days occurred less frequently with 7+3 than with aza-ven (71.6% vs 84.5%; RD −12.86%, 95% CI −23.91% to −1.82%; RR 0.85, 95% CI 0.74–0.97; p=0.046), while hospitalization between days 31–180 was identical in both groups (50.0% vs 50.0%; p=1.00). Infection between days 14–30 occurred in 34.7% versus 43.1%, respectively (RD −8.42%, 95% CI −22.62% to 5.78%; p=0.24). Conclusions: In this real-world cohort of patients with CML transformed to AML, azacitidine plus venetoclax achieved comparable 1-year survival and early infectious outcomes to intensive 7+3 induction despite being used in a frailer population. Larger multicenter studies are needed to confirm comparative effectiveness and refine patient selection.
Bhinder et al. (2026) studied this question.