Venetoclax Combined With Chemotherapy in Pediatric and Adolescent/Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia.

BACKGROUND

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and although many patients respond to induction therapy, those who relapse or have refractory disease face a poor prognosis. Venetoclax has promising preclinical and clinical activity in ALL. Here, we report the safety and preliminary efficacy of venetoclax combined with chemotherapy in pediatric and adolescent/young adult patients with relapsed/refractory ALL.

PROCEDURE: This phase 1, open-label, two-part, multicenter study evaluated venetoclax combined with chemotherapy in pediatric and adolescent/young adult patients (<25 years of age) with relapsed/refractory ALL. The study is registered with ClinicalTrials.gov, NCT03236857.

RESULTS

Thirty-one patients were treated and received venetoclax monotherapy (n = 1), venetoclax plus dexamethasone and/or vincristine and/or pegasparaginase (VXL; n = 20) or venetoclax plus cytarabine and/or etoposide and/or pegasparaginase (n = 10). Patients were heavily pretreated, with a median of 3 prior lines of therapy. The most common grade 3/4 treatment-emergent adverse event was febrile neutropenia (55%). One fatal adverse event possibly related to venetoclax occurred. The overall response rate of treated patients was 42%, with all responding patients achieving complete remission/complete remission with incomplete marrow recovery. In biomarker-evaluable patients, responses to venetoclax plus VXL-based or cytarabine-based chemotherapy were observed in patients harboring a range of genetic alterations and heterogeneous BH3 family member dependencies.

CONCLUSIONS

Venetoclax plus VXL-based or cytarabine-based chemotherapy was overall well tolerated, with promising preliminary efficacy.