Venetoclax and navitoclax in combination with chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma

Vinod A. Pullarkat, Norman J. Lacayo, Elias Jabbour, Jeffrey E. Rubnitz, Ashish Bajel, Theodore W. Laetsch, Jessica Leonard, Susan I. Colace, Seong Lin Khaw, Shaun A. Fleming, Ryan J. Mattison, Robin Norris, Joseph T. Opferman, Kathryn G. Roberts, Yaqi Zhao, Chunxu Qu, Mohamed Badawi, Michelle Schmidt, Bo Tong, John C. PeskoYan Sun, Jeremy A. Ross, Deeksha Vishwamitra, Lindsey Rosenwinkel, Su Young Kim, Amanda Jacobson, Charles G. Mullighan, Thomas B. Alexander, Wendy Stock

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/ BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population.

Original languageEnglish (US)
Pages (from-to)1440-1453
Number of pages14
JournalCancer discovery
Volume11
Issue number6
DOIs
StatePublished - 2021

ASJC Scopus subject areas

  • Oncology

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