FDA Approval: Venetoclax in Combination for Newly-diagnosed Acute Myeloid Leukemia

The Food and Drug Administration (FDA) granted regular approval to Venetoclax in combination with medications azacitidine, decitabine, or low-dose cytarabine (LDAC) for newly-diagnosed acute myeloid leukemia (AML) in adults aged 75 years or above, or who have comorbidities that preclude the use of intensive induction chemotherapy. 
 
Venetoclax Tablets were initially granted accelerated approval for this indication in the month of November 2018. Efficacy was confirmed in a couple of randomized, double-blind, placebo-controlled carried out trials (VIALE-A & VIALE-C) in patients with Acute Myeloid Leukemia (AML). 

Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a type of blood cancer. It starts in your bone marrow, the soft inner parts of bones. AML usually begins in cells that turn into white blood cells. With acute types of leukemia such as AML, bone marrow cells don't grow the appropriate way. 
 
In the carried out trial named VIALE-A, patients were given venetoclax in combination with azacitidine (n=286) or placebo in combination with azacitidine (n=145). The efficacy was established based on an improvement in OS.

Specifically, the median overall survival was 14.7 months (95 percent CI: 11.9, 18.7) in patients treated with venetoclax in combination with azacitidine compared to 9.6 months (95 percent CI: 7.4, 12.7) in those who receiving placebo along with azacitidine (HR 0.66; 95 percent CI: 0.52, 0.85; p<0.001). 
 
Patients treated with venetoclax in combination with azacitidine also demonstrated an enhancement in CR rate: 37 percent (95 percent CI: 31 percent, 43 percent) versus 18 percent (95 percent CI: 12 percent, 25 percent).
 
In the carried out trial named VIALE-C, patients were given venetoclax in combination with low-dose cytarabine (n=143) or placebo along with low-dose cytarabine (n=68). Efficacy was based on CR rate and time-span of CR. 
 
CR rate on the venetoclax in combination with low-dose cytarabine arm was noted 27 percent (95 percent CI: 20 percent, 35 percent) with a median time-span of 11.1 months (95 percent CI: 6.1, not reached) in comparison to 7.4 percent (95 percent CI: 2.4 percent, 16 percent) with a median time-span of 8.3 months (95 percent CI: 3.1, not reached) in those who receiving placebo in combination with low-dose cytarabine. Venetoclax in combination with low-dose cytarabine did not significantly improve Overall Survival vs placebo plus low-dose cytarabine  (HR 0.75; 95 percent CI 0.52, 1.07; p=0.114). 
 
With regard to safety, the most commonly reported side effects or toxicities with the venetoclax combination include fatigue, nausea, diarrhea, constipation, neutropenia, thrombocytopenia and febrile neutropenia. 
 Other side effects include pneumonia, vomiting, edema, hemorrhage, pyrexia, dyspnea, anemia, rash, abdominal pain, musculoskeletal pain, dizziness, oropharyngeal pain, cough, sepsis, and hypotension. 

Reference:

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-venetoclax-combination-untreated-acute-myeloid-leukemia