The Food and Drug Administration (FDA) approved Revuforj (revumenib) for the treatment of adults and children aged 1 year and older with relapsed or refractory acute leukemia with a KMT2A translocation.
Of note, translocation refers to a genetic change when a piece of chromosome breaks off and then attaches to another chromosome.
The approval, which was announced in a notice from the FDA, was based on findings from the AUGMENT-101 trial including 104 adult and pediatric patients with relapsed or refractory acute leukemia with a KMT2A translocation. Notably, patients with an 11q23 partial tandem duplication were excluded. A partial tandem duplication is when a segment of DNA is duplicated and inserted next to the original sequence, which can disrupt normal cellular processes.
Patients in the AUGMENT-101 trial were treated with Revuforj until unacceptable toxicity, disease progression, hematopoietic stem cell transplantation or failure to achieve morphological leukemia-free state by four cycles of treatment, according to the notice. Morphological leukemia-free state is when a patient with leukemia no longer exhibits any abnormal blood cells or bone marrow cells characteristic of the disease.
The main areas of interest in the trial were complete remission plus complete remission with partial hematological recovery, conversion from transfusion dependence to independence and duration of complete remission plus complete remission with partial hematological recovery, which is when all signs of leukemia have disappeared, although the patient’s blood cell counts have not fully recovered.
Of the patients in the AUGMENT-101 trial, 21.2% achieved complete remission plus complete remission with partial hematological recovery with a median duration of 6.4 months. In addition, of the 22 patients who achieved either complete response or complete remission with partial hematological recovery, the median time to either of those outcomes was 1.9 months.
Trial findings also demonstrated that of the 83 patients who were dependent on red blood cell and/or platelet transfusions at the start of the trial, 14% because independent of red blood cell and platelet transfusions during the 56-day period after the start of the trial, according to the notice. In addition, of the 21 patients who were independent of both red blood cell and platelet transfusions at the start of the study, 48% remained independent of transfusions during this time period after the start of the study.
The most common side effects, which occurred in at least 20% of patients, included nausea, bleeding, musculoskeletal pain, high phosphate levels, increased aspartate aminotransferase, infection, febrile neutropenia, increased intact parathyroid hormone, increased alanine aminotransferase, diarrhea, bacterial infection, QT prolongation, differentiation syndrome, increased triglycerides, decreased phosphate, decreased potassium, constipation, decreased appetite, fatigue, viral infection and increased alkaline phosphatase.
The FDA noted that the recommended dose of Revuforj can vary based on a patient’s weight and simultaneous use of CPT3A4 inhibitors. In addition, there is an anticipated delay in commercial availability of the lowest-dose strength of Revuforj, for use in patients who weigh less than 40 kilograms. Because of this, Revuforj will be available via an expanded access program to allow for dosing for those specific patients.
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