Sonrotoclax plus azacitidine induces remission in acute undifferentiated leukemia case

A 56-year-old man with newly diagnosed acute undifferentiated leukemia (AUL) achieved morphological complete remission with incomplete hematologic recovery after a single induction cycle of sonrotoclax combined with azacitidine, according to a case report published in Annals of Hematology. At post-treatment reassessment, the authors confirmed deep remission with negative measurable residual disease. The report describes what its authors call a promising therapeutic strategy for a malignancy that currently has no standardized first-line treatment.

AUL is a rare and highly aggressive hematologic malignancy with a dismal prognosis. Conventional acute myeloid leukemia (AML)-type or acute lymphoblastic leukemia (ALL)-type chemotherapy yields low remission rates in this disease, and most patients fail to achieve sufficient disease control to bridge to curative allogeneic hematopoietic stem cell transplantation. This treatment gap leaves patients with few established options once standard induction approaches fall short.

The patient in this case harbored mutations in three genes: TET2, DNMT3A and U2AF1. He received induction therapy with sonrotoclax, described in the report as a novel inhibitor of B-cell lymphoma-2 (BCL-2), given together with azacitidine. The authors suggest that this combination may be a particularly suitable strategy for AUL patients with epigenetic driver mutations, the category into which they place the mutations observed in this patient.

The remission achieved was both rapid and deep. Morphological complete remission with incomplete hematologic recovery, abbreviated CRi, was reached after one induction cycle, meaning the leukemia was no longer detectable morphologically although hematologic recovery remained incomplete. At the post-treatment reassessment, deep remission was confirmed with negative measurable residual disease, indicating that no residual disease was detected by residual disease testing at that time point.

The primary adverse events observed during treatment were myelosuppression and febrile neutropenia. Both complications were well controlled with supportive care, according to the report. The authors do not report any discontinuation of the regimen in this case, and the abstract identifies myelosuppression and febrile neutropenia as the primary adverse events encountered during the induction period.

The authors conclude that this single case suggests sonrotoclax plus azacitidine represents a promising therapeutic strategy for AUL, particularly in patients with epigenetic driver mutations such as those seen here. They explicitly caution, however, that further large-scale studies are required to verify the long-term efficacy and safety of this regimen before any broader conclusions can be drawn from one patient’s outcome.

As a case report, the evidence is limited to a single patient and cannot establish how often this approach would succeed across the wider AUL population. The open-access article, shared early as a peer-reviewed accepted version carrying a permanent DOI, adds AUL to the diseases being explored with the targeted combination of a novel BCL-2 inhibitor and azacitidine rather than conventional AML-type or ALL-type chemotherapy alone.

Subject of Research: Case report of sonrotoclax combined with azacitidine for acute undifferentiated leukemia

Article Title: Case Report: Sonrotoclax in combination with azacitidine for acute undifferentiated leukemia

Article References: Cheng, C., Mi, R., Li, D., Chen, L., Wang, L., & Wei, X. (2026). Case Report: Sonrotoclax in combination with azacitidine for acute undifferentiated leukemia. Annals of Hematology. https://doi.org/10.1007/s00277-026-07262-z

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DOI: 10.1007/s00277-026-07262-z

Keywords: acute undifferentiated leukemia, sonrotoclax, azacitidine, BCL-2 inhibitor, measurable residual disease, case report, Annals of Hematology, hematology, leukemia, targeted therapy, Case, Report