Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)

Abstract

T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS) is an uncommon and aggressive leukemia without well-established treatment guidelines, particularly when relapsed. Venetoclax plus a hypomethylating agent offers a promising option in this situation since studies support its use in both acute myeloid and, albeit with fewer data to date, acute T-cell-lymphoblastic leukemias. We report the successful eradication of T/myeloid MPAL NOS relapsed after allogeneic stem cell transplant with venetoclax plus decitabine. A consolidative allogeneic stem cell transplant from a second donor was subsequently performed, and the patient remained without evidence of disease more than one year later. Further investigation is indicated to evaluate venetoclax combined with hypomethylating agents and/or other therapies for the management of T/myeloid MPAL NOS.

Multilineage Lymphoblastic Lymphoma as an Initial Presentation of Mixed Phenotype Acute Leukemia

“…In addition, several case reports describe the efficacy of venetoclax combined with hypomethylating agents such as azacitidine and decitabine in MPAL that did not respond to conventional chemotherapy [ 14 – 16 ]. However, only one case of T/myeloid MPAL has been reported, in which venetoclax combined with decitabine showed efficacy [ 16 ]. To the best of our knowledge, our report presents the first case of MPAL T/myeloid NOS, in which venetoclax and azacitidine therapy was effective in achieving remission.…”

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis and Therapeutic Strategies

“…CAR-T therapy engineered to target CD19-positive blasts is an emerging option with some success in case reports [ 62 , 63 ]. Venetoclax, which targets BCL-2, combined with various chemotherapies in MPAL, has shown encouraging results in recent case series [ 39 , 64 , 65 ]. Magrolimab, a macrophage checkpoint inhibitor targeting CD 47, in combination with azacytidine, has shown promising activity in high-risk AML.…”

Venetoclax Combined with Hypomethylating Agents for Treatment-Naïve B/Myeloid Mixed Phenotype Acute Leukemia

“…In ALL, two reported cases of T-ALL who relapsed after HSCT were treated with venetoclax and decitabine and achieved second CR [ 19 , 20 ]. Two cases of relapsed or refractory T/myeloid MPAL were reported to receive venetoclax combined with azacitidine or decitabine, both induced CR [ 21 , 22 ]. In our female patient, whose lymphoid-linage blasts dominated, this combinational regimen did show efficacy at cycle 1 induction therapy, particularly for myeloid-linage aberrant cells, whereas the lymphoid blasts relapsed after the consolidation cycle.…”