Venetoclax/Venetoclax may be an option for children with MDS R/R AML

Pediatric patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) may benefit from venetoclax, a new study suggests. This report comes from a single-center study in which 12 patients received a venetoclax-based treatment regimen under a compassionate use program. There is no universal standard of care for R/R AML. The BCL-2 inhibitor venetoclax has become a first-line option for some adults with newly diagnosed AML, in combination with hypomethylating agents (HMAs) or low-dose cytarabine, and was approved by the U.S. Food and Drug Administration (FDA) in 2018.

A 2020 report found that in pediatric patients with severely relapsed and refractory AML using the recommended phase 2 dose of 360 mg/m2, the overall response rate (ORR) of venetoclax plus chemotherapy was 80% (95% CI, 56%-94%) and the complete response rate (CR) was 70% (95% CI, 46%-88%). Subsequent studies of venetoclax in children showed that the therapy works best when combined with other treatments, has a good safety profile, and can serve as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT).

In the new report, researchers analyzed the cases of 12 patients aged 2 to 12 years who received a venetoclax-based regimen for R/R myeloid malignancies. Eight of the patients had previously relapsed, five were taking venetoclax after allogeneic hematopoietic stem cell transplantation, and three had refractory AML. One patient had MDS-associated AML (MDS-AML) and the remaining patients had R/R AML. Patients received venetoclax plus HMAs (five patients) or chemotherapy (five patients) or venetoclax alone (two patients).

At a median follow-up of 11 months, the researchers said the ORR for this cohort was 41.6%, with 33% of patients achieving CR. Patients who received venetoclax in combination with cytotoxic drugs had the highest CR rate (60%). Only 1 patient who received venetoclax plus HMAs had a complete response, but recovery was incomplete. Neither of the 2 patients who received monotherapy had a response. The 1-year overall survival rate was 50% (95% CI, 28%-88%), and the 1-year event-free survival rate was 25% (95% CI, 9.4%-67%). At the end of follow-up, 11 patients died. Most patients died from progression or recurrence (10 patients), but 1 patient died from a transplant-related infection.

The single-center nature of this study limits the conclusions that can be drawn from it, but these data nevertheless provide valuable insights. For example, Four patients achieved complete remission without anthracyclines, and three of them were able to undergo hematopoietic stem cell transplantation. This regimen may be particularly beneficial in heavily pretreated patients and may provide a less intensive treatment option. Cytarabine-based venetoclax regimen is a bridging strategy that favors hematopoietic stem cell transplantation. Additionally, more studies are needed to understand the molecular determinants of response to venetoclax-based treatment regimens and indicate the need to develop resistance management strategies.

BLC2 inhibitors like venetoclaxBLC2 inhibitors are promising targeted therapies for the treatment of R/R myeloid diseases, but extensive research efforts and multicenter clinical trials are needed to refine treatment strategies for these patients.

Venetoclax/Venetoclax,

Reference materials:https://www.ajmc.com/view/venetoclax-may-be-an-option-for-children-with-r-r-aml-mds