CB-103: A novel CSL-NICD inhibitor for the treatment of NOTCH-driven T-cell acute lymphoblastic leukemia: A case report of complete clinical response in a patient with relapsed and refractory T-ALL

Michael Medinger; Till Junker; Dominik Heim; Alexandar Tzankov; Philip M Jermann; Maria Bobadilla; Michele Vigolo; Rajwinder Lehal; Florian D Vogl; Michael Bauer; Jakob Passweg

doi:10.1002/jha2.510

CB-103: A novel CSL-NICD inhibitor for the treatment of NOTCH-driven T-cell acute lymphoblastic leukemia: A case report of complete clinical response in a patient with relapsed and refractory T-ALL

EJHaem. 2022 Jun 16;3(3):1009-1012. doi: 10.1002/jha2.510. eCollection 2022 Aug.

Authors

Michael Medinger^{1

2}, Till Junker^{1

2}, Dominik Heim^{1

2}, Alexandar Tzankov^{2

3}, Philip M Jermann³, Maria Bobadilla⁴, Michele Vigolo⁴, Rajwinder Lehal⁴, Florian D Vogl⁴, Michael Bauer⁴, Jakob Passweg^{1

2}

Affiliations

¹ Department of Hematology University Hospital Basel Basel Switzerland.
² University Basel Basel Switzerland.
³ Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland.
⁴ Cellestia Biotech AG Basel Switzerland.

Abstract

Relapsed T cell acute lymphoblastic leukaemia (T-ALL) has a very poor prognosis. A 24-year-old patient with relapsed high-risk T-ALL (PTEN gene deletion; NOTCH1 mutation), was treated with the NOTCH inhibitor CB-103. Within 1 week of starting CB-103, the bone marrow was free of T-ALL blast infiltration (MRD+) and successfully underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Sequential samples of ctDNA to monitor the disease after allo-HSCT showed a decrease of circulating Notch1 and PTEN alterations. This is the first T-ALL patient treated with CB-103. The observed clinical response encourages further exploration of CB-103 in ALL.

Keywords: NOTCH inhibition; acute lymphoblastic leukaemia; allogeneic hematopoietic stem cell transplantation.

Publication types

Case Reports