Can BCT-100 be safely combined with low-dose cytarabine for older patients with acute myeloid leukemia that cannot receive intensive therapy?

This study compared the effectiveness and safety of low-dose (LD) cytarabine (Ara-C; Cytosar-U) with recombinant arginase BCT-100 (BCT-100) to Ara-C alone in older patients with acute myeloid leukemia (AML) that were unsuitable for intensive therapy. The data showed that LD Ara-C (LDAC) combined with BCT-100 resulted in similar toxicity and overall survival (OS) levels to Ara-C alone and can be used in older patients with AML for which intensive therapy is not appropriate.

AML is a bone marrow and blood cancer commonly affecting children and adults. AML cause the formation of under-developed, abnormal white blood cells (“blasts”). Blasts prevent normal blood cell production. Arginine, a protein-building block (amino acid), supports blast cell multiplication.

Older adults with AML are not eligible for the use of intensive chemotherapy for remission induction. Suitable treatment options include venetoclax (Venclexta)-based combinations with LDAC or hypomethylating agents (HMAs; a type of chemotherapy). However, relapses frequently occur, and long-term survival is uncommon. Newer options to improve patient outcomes are needed.

BCT-100 is a human recombinant arginase (an enzyme) that rapidly reduces arginine and interferes with the multiplication of AML blasts. There is a need to investigate the effect of a combination of LDAC and BCT-100 in the treatment of AML in patients over 60 years of age that are unsuitable for intensive chemotherapy.

This study included 81 patients with AML that were over 60 years of age. Group 1 included 40 patients who randomly received subcutaneous (SC) injections of LDAC at 20 mg, twice daily, for 10 days. Group 2 included 41 patients who were randomly given SC injections with LDAC at 20 mg, twice daily, for 10 days in combination with intravenous BCT-100 at 1600 units/kg on days 1, 8, 15, and 22. Patients were followed-up for an average of 23.4 months.

An overall response rate occurred in 19.5% of patients in group 2 and 15% of the patients in group 1. This difference was not considered statistically significant. All 19.5% of patients in group 1 had a complete response (disappearance of all cancer cells). 7.5% of the 15% in group 1 had a complete response.

Average overall survival was similar between group 1 (6.4 months) and group 2 (4.3 months). Group 2 had a slight improvement in survival without relapse (by 52%) compared to group 1. Both groups had a low occurrence of serious side effects. The addition of BCT-100 did not result in an increase in side effects compared to group 1. 

The study concluded that BCT-100 can be safely added to LDAC in patients with AML that cannot undergo intensive therapy.  

The study had a very small number of participants and a short follow-up period. Further studies are needed.