CD38 antibodies in multiple myeloma: back to the future

CD38 is highly and uniformly expressed on multiple myeloma (MM) cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of nonhematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as a receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune-effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38+ immune-suppressor cells. CD38-targeting antibodies are generally well tolerated and induce partial response or better in ~30% of heavily pretreated MM patients as monotherapy. Based on their distinct mechanisms of action, favorable toxicity profile, and single-agent activity, CD38 antibodies are attractive partners in combination regimens. Indeed, deep responses and prolonged progression-free survival can be achieved in relapsed/refractory MM patients when CD38 antibodies are combined with immunomodulatory agents or proteasome inhibitors. Infusion-related reactions, which typically occur during the first infusion, are the most frequent adverse events. Attention should also be paid to the interference of CD38 antibodies with certain laboratory assays, which may complicate response evaluation and blood compatibility testing. Several ...
Source: Blood - Category: Hematology Authors: Tags: Free Research Articles, Lymphoid Neoplasia, Review Articles, Review Series, Clinical Trials and Observations Source Type: research

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Conditions:   Accelerated Phase Chronic Myelogenous Leukemia;   Adult Acute Lymphoblastic Leukemia in Remission;   Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities;   Adult Acute Myeloid Leukemia With Del(5q);   Adult Nasal Type Extranodal NK/T-cell Lymphoma;   Anaplastic Large Cell Lymphoma;   Angioimmunoblastic T-cell Lymphoma;   Blastic Phase Chronic Myelogenous Leukemia;   Childhood Acute Lymphoblastic Leukemia in Remission; &...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Accelerated Phase Chronic Myelogenous Leukemia;   Adult Acute Lymphoblastic Leukemia in Remission;   Adult Acute Myeloid Leukemia in Remission;   Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities;   Adult Acute Myeloid Leukemia With Del(5q);   Adult Acute Myeloid Leukemia With Inv(16)(p13;q22);   Adult Acute Myeloid Leukemia With t(15;17)(q22;q12);   Adult Acute Myeloid Leukemia With t(16;16)(p13;q22);   Adult Acute Myeloid Leukemia With t(8;21)(q22;q22);  ...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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