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Isatuximab in combination with cemiplimab in patients with relapsed/refractory multiple myeloma: A phase 1/2 study
A. Lesokhin, R. LeBlanc, MA. Dimopoulos, M. Capra, C. Carlo-Stella, L. Karlin, JF. Castilloux, P. Forsberg, G. Parmar, A. Tosikyan, L. Pour, V. Ribrag, R. Ribolla, AO. Abdallah, N. Le Roux, L. Dong, H. van de Velde, L. Mayrargue, L. Lépine, S....
Language English Country United States
Document type Clinical Trial, Phase II, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't
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PubMed
36866838
DOI
10.1002/cam4.5753
Knihovny.cz E-resources
- MeSH
- Dexamethasone therapeutic use MeSH
- Antibodies, Monoclonal, Humanized adverse effects MeSH
- Humans MeSH
- Multiple Myeloma * drug therapy MeSH
- Antineoplastic Agents * therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Clinical Trial, Phase II MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Given the incurable nature of multiple myeloma (MM), efforts are made to improve the efficacy of anti-CD38 monoclonal antibodies via combinations with other potentially synergistic therapies. This Phase 1/2 trial (NCT03194867) was designed to determine whether cemiplimab (anti-PD-1) enhances the anti-myeloma activity of isatuximab (anti-CD38) in patients with relapsed and refractory multiple myeloma (RRMM), to confirm the feasibility of the combination, determine its efficacy, and further evaluate its safety. METHODS: Patients received isatuximab 10 mg/kg once weekly for 4 weeks followed by every 2 weeks (Isa), or isatuximab 10 mg/kg plus cemiplimab 250 mg every 2 (Isa + CemiQ2W) or every 4 weeks (Isa + CemiQ4W). RESULTS: Overall, 106 patients with RRMM treated with a median of 4 prior lines were included; 25.5% had high-risk cytogenetics, 63.2% were refractory to proteasome inhibitors and immunomodulatory agents, 26.4% were previously exposed to daratumumab, and 84.0% were refractory to their last treatment line. There were no major changes in the safety or pharmacokinetic profile of isatuximab with the addition of cemiplimab. As assessed by investigators, four patients (11.8%) in the Isa arm, nine patients (25.0%) in the Isa + CemiQ2W arm, and eight patients (22.2%) in the Isa + CemiQ4W arm were responders. Though response rates were numerically higher in cemiplimab-containing arms, differences were not statistically significant and did not translate to improved progression-free or overall survival after a median follow-up of 9.99 months. CONCLUSION: Our results suggest a marginal benefit by adding cemiplimab to isatuximab, despite demonstration of target engagement, without additional observed safety issues.
Centro Integrado de Hematologia e Oncologia Hospital Mãe de Deus Porto Alegre Brazil
Department of Biomedical Sciences Humanitas University Rozzano Milan Italy
Department of Clinical Therapeutics National and Kapodistrian University of Athens Athens Greece
Department of Haematology Wollongong Hospital Wollongong New South Wales Australia
Department of Hematology ASST Spedali Civili di Brescia Brescia Italy
Department of Hematology Gustave Roussy Université Paris Saclay Villejuif France
Department of Internal Medicine University Hospital Brno Brno Czech Republic
Department of Oncology and Hematology IRCCS Humanitas Research Hospital Rozzano Milan Italy
Hematology Department CHU Nantes Nantes France
Hôpital du Sacré Coeur de Montréal Montréal Qubec Canada
Sanofi Cambridge Massachusetts USA
Sanofi Clinical Pharmacokinetics on behalf of Excelya Chilly Mazarin France
Sanofi Research and Development Chilly Mazarin France
Sanofi Research and Development on behalf of Altran Vitry sur Seine France
References provided by Crossref.org
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