Venetoclax as Salvage Treatment for Relapsed/Refractory B-ALL Post-CAR-T Therapy

Despite high early response rates following chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory pediatric B-cell acute lymphoblastic leukemia (B-ALL), many patients relapse, and downregulation of the antigen targeted by the CAR-T has emerged as a major challenge. Furthermore, minimal residual disease (MRD) screening using next-generation sequencing (NGS) does not inform antigen status. In cases of either antigen downregulation or unknown antigen status, there is a need for antigen-agnostic salvage agents such as venetoclax. Data regarding venetoclax use in the post-CAR-T setting, however, remain limited.

We conducted a retrospective study of patients with B-ALL who received CAR-T therapy followed by venetoclax from nine tertiary pediatric oncology centers in the United States.

Nineteen patients received venetoclax for treatment of relapsed/refractory (R/R) B-ALL following CAR-T therapy. The median number of relapses pre-venetoclax was 2 (range, 1-5). Of 12 patients with known antigen expression status at venetoclax initiation, 11 (92%) had antigen downregulation. Side effects of venetoclax monotherapy were nausea (100%) and rash (25%); in combination chemotherapy, cytopenias (63%) and infections (42%) were also reported. No patient deaths occurred from venetoclax toxicity. After venetoclax, 8 of 19 patients (42%) achieved either morphologic complete remission (CR) or clearance of prior MRD. Of 11 patients with baseline MRD-only disease, 4 (36%) achieved MRD negativity. Of 8 patients with baseline morphologic disease, 2 (25%) achieved morphologic CR. Patients with antigen downregulation had a 29% morphologic CR rate.

Our experience suggests tolerability and promise of venetoclax in pediatric R/R B-ALL, including patients with antigen downregulation.