New AML Regimen for Unfit Patients Gets FDA’s Blessing

The FDA on Wednesday approved a new all-oral regimen for newly diagnosed acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy.

The combination of decitabine-cedazuridine (Inqovi) plus venetoclax (Venclexta) is specifically indicated for either adults 75 and older or those whose comorbidities would preclude an intensive induction regimen — a group that comprises over half of the more than 20,000 people diagnosed with AML each year in the U.S.

Support came from ASCERTAIN-V, an open-label, single-arm, phase II trial involving 101 adults. Treatment with the regimen induced complete remissions (CRs) in 41.6%, with durations of CR ranging from 0.5 to 16.3 months (median not reached). Median time to CR was 2 months.

Another phase II study in a similar population reported a 64% response rate with decitabine-cedazuridine plus venetoclax, including 57% who had CRs or CRs with incomplete recovery. Among those with a CR or CR with incomplete recovery, the median duration of response reached 13.2 months.

According to the labeling, adverse events (AEs) occurring in 20% or more of the AML patients treated with decitabine-cedazuridine plus venetoclax included neutropenia, febrile neutropenia, thrombocytopenia, hemorrhage, anemia, bacterial and viral infections, diarrhea, fatigue, mucositis, constipation, arthralgia, decreased appetite, edema, nausea, dyspnea, decreased white blood cell counts, sepsis, pneumonia, rash, transaminitis, myalgia, arrhythmia, and abdominal pain.

Common grade 3/4 laboratory abnormalities included decreases in leukocytes, lymphocytes, platelets, and hemoglobin.

Serious AEs occurred in 82% of patients, and included febrile neutropenia (31%), sepsis (22%), pneumonia (15%), infections (10%), hemorrhage (9%), and dyspnea (6%). Fatal AEs occurred in 8%.

Warnings and precautions in the prescribing information also note risks for myelosuppression and embryo-fetal toxicity.

The FDA first approved decitabine-cedazuridine in 2020 for adults with intermediate- and high-risk myelodysplastic syndromes and chronic myelomonocytic leukemia. Venetoclax carries indications for newly diagnosed unfit AML (in combination with azacitidine, decitabine, or low-dose cytarabine) and for chronic lymphocytic leukemia or small lymphocytic lymphoma.