Orlando, Florida—Findings being presented at the 2019 ASH Annual Meeting demonstrate that vosaroxin and infusional cytarabine is a safe treatment regimen for newly diagnosed patients with acute myeloid leukemia (AML).

“Until recently, the anthracycline and cytarabine based induction remained unchanged for over 4 decades. Vosaroxin…is a first-in-class anticancer quinolone derivative which is thought to induce less cardiac toxicity than standard anthracycline therapy,” explained Stephen Strickland, MD, Vanderbilt University Medical Center, Nashville, Tennessee, and co-investigators regarding the importance of evaluating this regimen for patients with AML.

Citing the VALOR trial, which showed improved complete response (CR) in relapsed/refractory AML with intermediate dose cytarabine and vosaroxinbut not an overall survival benefit, the VITAL trial was conducted to assess the combination of infusion cytarabine with vosaroxinin newly-diagnosed AML

The 2-stage phase 2 trial by Dr Strickland, et al, enrolled 42 patients aged 18 to 54 years with intermediate or high-risk disease and aged 55 years or older with any risk disease. There were 40 (95%) patients with intermediate or poor-risk AML. 

Treatment consisted of vosaroxin90mg/m2on days 1 and 4 and a continuous infusion of cytarabine 100 mg/m2on days 1 through 7.

A CR was required in 40% of patients in stage 1 of the study before the investigators could proceed with stage 2; of note, an additional 24 patients were added in stage 2. 

Ultimately, 48% of patients achieved a CR, and a further 3 patients had CRs with incomplete count recovery (CRi). By risk level, CR/CRi was seen in 73% of all intermediate-risk patients and 45% of poor-risk patients.

Furthermore, among patients with AML andTP53 mutations, the CR/CRi rate was 40%.

Notably, 45% of all patients underwent allogeneic hematopoietic stem cell transplantation. At the 1-year follow-up, the median progression-free survival was 43% and OS was 48% among all patients in the study.

The most common adverse events reported were thrombocytopenia (76%), anemia (64%), infection (62%), diarrhea (59%), leukopenia (53%), and oral mucositis (38%). 

“Largely I would say that the adverse events that we noticed were expected, for the most part, for patients receiving intensive induction strategies,” noted Dr Strickland at the presentation.

The investigators observed 3 grade 5 adverse events, and no incidence of cardiac toxicity. 

“Vosaroxin and infusional cytarabine is a clinically active induction regimen which warrants further investigation based on response rates and toxicity profile at least similar to current anthracycline based induction strategies with an apparent absence of cardiac toxicity,” concluded Dr Strickland and colleagues.—Kaitlyn Manasterski

Strickland SA, Podoltsev N, Mohan S. et al. The VITAL Trial: Phase II Trial of Vosaroxin and Infusional Cytarabine for Frontline Treatment of acute Myeloid Leukemia. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 180.