Targeting CD38 for acute leukemia

Abstract

Acute leukemia (AL) is a hematological malignancy, and the prognosis of most AL patients hasn’t improved significantly, particularly for relapsed or refractory (R/R) AL. Therefore, new treatments for R/R adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are urgently necessary. Novel developments have been made in AL treatment, including target and immune therapies. CD38 is one of the targets due to its high expression in many hematological malignancies, including multiple myeloma, ALL and a subset of AML. Consequently, targeting CD38 therapies, including CD38 monoclonal antibodies (mAbs), bispecific antibodies, and CAR-T cell therapy, exhibit promising efficacy in treating multiple myeloma without significant toxicity and are being explored in other hematological malignancies and nonhematological diseases. Herein, this review focuses on targeting CD38 therapies in ALL and AML, which demonstrate sound antileukemic effects in acute leukemia and are expected to become effective treatment methods.

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

“…6,7,9,10,18 CD38 is also expressed in other hematologic malignancies, such as chronic lymphocytic leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia, Waldenström's macroglobulinemia, and NK/T-cell lymphoma. 19,20 The role of CD38 antibodies in treating these malignancies is being actively investigated. In preclinical studies, both daratumumab and isatuximab inhibited the growth of T-ALL cell lines in vitro.…”

“…In preclinical studies, both daratumumab and isatuximab inhibited the growth of T-ALL cell lines in vitro. 20 One Phase 2 study has investigated daratumumab monotherapy for patients with relapsed/refractory NK/T-cell lymphoma, with an overall response rate (ORR) of 25% but a short median duration of response. 21 Case studies with daratumumab for the treatment of ALL have also been published, showing that some patients achieve minimal residual disease negativity (MRD−).…”

“…21 Case studies with daratumumab for the treatment of ALL have also been published, showing that some patients achieve minimal residual disease negativity (MRD−). 20 There is also the potential to target CD38 in the treatment of cutaneous T-cell lymphomas (CTCL), due to its dominant expression in some aggressive subtypes of CTCL. 22 In patients with CTCL, expression levels of CD38, as detected by immunohistochemistry were also negatively correlated with overall survival.…”

“…The role of CD38 antibodies in treating these malignancies is being actively investigated. In preclinical studies, both daratumumab and isatuximab inhibited the growth of T‐ALL cell lines in vitro 20 . One Phase 2 study has investigated daratumumab monotherapy for patients with relapsed/refractory NK/T‐cell lymphoma, with an overall response rate (ORR) of 25% but a short median duration of response 21 .…”

“…One Phase 2 study has investigated daratumumab monotherapy for patients with relapsed/refractory NK/T‐cell lymphoma, with an overall response rate (ORR) of 25% but a short median duration of response 21 . Case studies with daratumumab for the treatment of ALL have also been published, showing that some patients achieve minimal residual disease negativity (MRD−) 20 . There is also the potential to target CD38 in the treatment of cutaneous T‐cell lymphomas (CTCL), due to its dominant expression in some aggressive subtypes of CTCL 22 .…”