Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma

Martin, Thomas G.; Strickland, Stephen A.; Glenn, Martha; Charpentier, Eric; Guillemin, Hélène; Hsu, Karl; Mıkhael, Joseph

doi:10.1038/s41408-019-0198-4

Cited by 86 publications

(130 citation statements)

References 29 publications

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“…Isatuximab has been investigated as monotherapy for the treatment of RRMM in a phase 1/2 trial (ClinicalTrials.gov, NCT01084252) [34][35][36]. Martin and colleagues [35] evaluated isatuximab as monotherapy against RRMM in a phase 1 dose-escalation/expansion study, with the goal to determine the maximum tolerated dose of isatuximab. Overall, 84 patients with RRMM progressing on or after standard therapy received 0.0001-20 mg/kg of isatuximab intravenously (IV) weekly or every 2 weeks.…”

Section: Isatuximab Monotherapy Activity In MMmentioning

confidence: 99%

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Martin

Corzo

Chiron

et al. 2019

Cells

119

151

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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.

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Section: Isatuximab Monotherapy Activity In MMmentioning

confidence: 99%

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Martin

Corzo

Chiron

et al. 2019

Cells

119

151

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“…The other clinical grade anti-CD38 mAb, Isatuximab, is a human IgG1κ mAb under early clinical trials, in which it has shown meaningful anti-tumor activity [47,48]. Compared to Daratumumab, Isatuximab displays a stronger action of direct cell killing independent on cross-linking.…”

Section: Effects Of Cd38-directed Immunotherapy On Immune Cell Levelsmentioning

confidence: 99%

NK cells and CD38: Implication for (Immuno)Therapy in Plasma Cell Dyscrasias

Zambello

Barilà

Manni

et al. 2020

Cells

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Immunotherapy represents a promising new avenue for the treatment of multiple myeloma (MM) patients, particularly with the availability of Monoclonal Antibodies (mAbs) as anti-CD38 Daratumumab and Isatuximab and anti-SLAM-F7 Elotuzumab. Although a clear NK activation has been demonstrated for Elotuzumab, the effect of anti-CD38 mAbs on NK system is controversial. As a matter of fact, an initial reduction of NK cells number characterizes Daratumumab therapy, limiting the potential role of this subset on myeloma immunotherapy. In this paper we discuss the role of NK cells along with anti-CD38 therapy and their implication in plasma cell dyscrasias, showing that mechanisms triggered by anti-CD38 mAbs ultimately lead to the activation of the immune system against myeloma cell growth.

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“…A phase 1 dose-escalation/expansion study first evaluated isatuximab monotherapy (20 mg/kg the highest dose tested QW or Q2 W) in 84 patients with RRMM (NCT01084252) [60]. Maximum-tolerated dose (MTD) was not reached.…”

Section: Isatuximabmentioning

confidence: 99%

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

Musto

Rocca

2020

Expert Review of Hematology

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Introduction: In the last few years, monoclonal antibodies have rapidly modified the therapeutic strategies for treating patients with multiple myeloma. Areas covered: In this review, the most recent literature data regarding indications for which monoclonal antibodies are currently or will be shortly approved as salvage therapies in relapsed/refractory myeloma are discussed. In particular, updated results until March 22, 2020 of antibodies directed against CD38 (daratumumab and isatuximab), SLAMF7 (elotuzumab), BCMA (GSK2857916/belantamab mafodotin), and PD-1/PD-1 L axis (nivolumab and pembrolizumab) will be analyzed in detail. Expert opinion: Monoclonal antibodies represent a new, very effective approach that will open novel and dynamic treatment scenarios for myeloma patients in the coming years. Optimal positioning and selection of different antibodies that are or will be soon available, appropriate combinations and careful evaluation of possible new toxicities should be considered in the future management of these patients.

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Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma

Cited by 86 publications

References 29 publications

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

NK cells and CD38: Implication for (Immuno)Therapy in Plasma Cell Dyscrasias

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

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