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Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Hematology/Oncology, University of California San Francisco, San Francisco, CA 94143-0324, USA
Sanofi Oncology, Cambridge, MA 02142, USA
Translational and Experimental Medicine, Sanofi Research & Development, 94403 Vitry-sur-Seine, France
Integrated Drug Discovery, Sanofi Research & Development, 94403 Vitry-sur-Seine, France
Dana-Farber Cancer Institute, Boston, MA 02215, USA
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1522;
Received: 31 October 2019 / Revised: 22 November 2019 / Accepted: 23 November 2019 / Published: 26 November 2019
CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a suitable target for therapeutic antibodies. Several anti-CD38 therapies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab (SAR650984), respectively. Studies have shown that anti-CD38 therapies are effective in the treatment of relapsed/refractory MM and are well tolerated, with infusion reactions being the most common side effects. They can be used as monotherapy or in combination with immunomodulatory agents, such as pomalidomide, or proteasome inhibitors to potentiate their activity. Here we examine isatuximab and several anti-CD38 agents in development that were generated using new antibody engineering techniques and that may lead to more effective CD38 targeting. We also summarize trials assessing these antibodies in MM, other malignancies, and solid organ transplantation. Finally, we propose that further research on the mechanisms of resistance to anti-CD38 therapy and the development of biomarkers and new backbone regimens with CD38 antibodies will be important steps in building more personalized treatment for patients with MM. View Full-Text
Keywords: multiple myeloma; anti-CD38 therapy; isatuximab multiple myeloma; anti-CD38 therapy; isatuximab
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MDPI and ACS Style

Martin, T.G.; Corzo, K.; Chiron, M.; van de Velde, H.; Abbadessa, G.; Campana, F.; Solanki, M.; Meng, R.; Lee, H.; Wiederschain, D.; Zhu, C.; Rak, A.; Anderson, K.C. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab. Cells 2019, 8, 1522.

AMA Style

Martin TG, Corzo K, Chiron M, van de Velde H, Abbadessa G, Campana F, Solanki M, Meng R, Lee H, Wiederschain D, Zhu C, Rak A, Anderson KC. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab. Cells. 2019; 8(12):1522.

Chicago/Turabian Style

Martin, Thomas G., Kathryn Corzo, Marielle Chiron, Helgi van de Velde, Giovanni Abbadessa, Frank Campana, Malini Solanki, Robin Meng, Helen Lee, Dmitri Wiederschain, Chen Zhu, Alexey Rak, and Kenneth C. Anderson. 2019. "Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab" Cells 8, no. 12: 1522.

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