Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Abstract

Venetoclax is approved for adult patients with chronic lymphocytic leukemia and acute myeloid leukemia. Expanding its use to the pediatric population is currently under investigation, but more robust data are needed. We retrospectively analyzed the safety and efficacy of venetoclax in children/AYA with ALL/LBL. We identified 18 patients (T-cell ALL, n = 7; T-cell LBL, n = 6; B-cell ALL, n = 5) aged 6-22 years. No new venetoclax safety signals were identified; the most common toxicity was myelosuppression. No deaths occurred within 30 days from the start of the therapy. A mean of 2.6 (range 0-8) prior lines of therapy were given. The mean duration of venetoclax was 4.06 months (range 0.2-24.67 months). Complete remission was achieved in 11 (61%) patients. Of the eight patients who remain alive, four are continuing on venetoclax combination therapy, and four proceeded to hematopoietic stem cell transplantation. Three patients who initially achieved CR, later relapsed, and are deceased. Nine patients are deceased, and one patient was lost to follow-up. Overall survival is 9.14 months (range 1.1-33.1), and progression-free survival is 7.34 months (range 0.2-33.1). This is the largest cohort of pediatric/AYA patients who received venetoclax for ALL/LBL. Our data support the consideration of venetoclax-based regimens in pediatric patients with R/R ALL/LBL and its investigation as upfront therapy for T-cell ALL/LBL.

Keywords: Bcl-2 inhibitor; acute lymphoblastic leukemia; early precursor T-cell; lymphoblastic lymphoma; venetoclax.

Figure 1

Kaplan–Meier curves for overall survival and progression-free survival. Survival proportions graphs from the start of venetoclax therapy to a major event, defined as progression or death. (A) Overall survival (OS) for all disease diagnoses. (B) Progression-free survival (PFS) for all disease diagnoses. (C) OS for T-cell LBL patients. (D) PFS for T-cell LBL patients. (E) OS for T-cell ALL patients. (F) PFS for T-cell ALL patients. (G) OS for B-cell ALL patients. (H) PFS for B-cell ALL patients.

Figure 2

PETCT response of a patient with lymphoblastic lymphoma after one cycle of venetoclax combination therapy. PETCT response of patient 2 (see Table 2), with lymphoblastic lymphoma after one cycle of venetoclax combination therapy.