Κατεύθυνση Κλινικές Μελέτες: Σχεδιασμός και ΕκτέλεσηLibrary of the School of Health Sciences
Ευάγγελος Τέρπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Φλώρα Ζαγουρή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Γαβριατοπούλου, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ο ρόλος των μονοκλωνικών αντισωμάτων anti-CD38 και anti-SLAMF7 στο πολλαπλό μυέλωμα: από τις προκλινικές μελέτες στις εγκρίσεις κυκλοφορίας
The role of anti-CD38 and anti-SLAMF7 monoclonal antibodies in the treatment of multiple myeloma: from the preclinical studies to the approvals
Introduction: Multiple myeloma is a plasma cell dyscrasia characterized as chronic and incurable with frequent periods of remission and relapse. In the last decade there has been significant progress in understanding the pathophysiology of the disease, which has led to the development of new, more effective and safer molecules that improve the quality of life of patients and extend their survival. Monoclonal antibodies are probably the fastest growing and most promising class of anti-myeloma drugs. They constitute the treatment of choice in patients with refractory or/and relapsed multiple myeloma and in newly diagnosed patients in combination with other antimyeloma agents.
Aim of the study: The aim of this study is the systematic review of the clinical trials that led to the FDA and EMA approval of two monoclonal antibodies, Daratumumab and Elotuzumab indicated in multiple myeloma.
Material-Methods: A Systematic literature research was performed on the Pub-Med and clinicaltrials.gov databases and the data from 15 clinical trials were included. In addition to the above, data were also extracted from 68 related published papers. For the purpose of this review, only clinical trials with completed data analysis and published results have been selected. The analysed studies are phase 1,2,3 or 4, with the enrollment period completed.
Results: The selected clinical trials led to the FDA and EMA approval of the analysed mAbs. Daratumumab was approved as monotherapy with ORR 29% and a mean PFS 3.7 months according to the SIRIUS study. As a combination therapy with Lenalidomide/dexamethasone with ORR 31% and mean PFS 3.8 months according to MMY3003 study, in combination with Bortezomib/dexamethasone with ORR 79.3% according to CASTOR study, in combination with Pomalidomide/dexamethasone with ORR 60% and mean PFS 8.8 months according to EQUULEUS study, in combination with Bortezomib/Melphalan/Prednisone with ORR 90.9% and mean PFS 71.6% according to ALCYONE study, and in combination with Bortezomib/thalidomide/dexamethasone according to CASSIOPEIA trial. Elotuzumab was approved as a combination therapy with Lenalidomide/Dexamethasone with PFS-ELd 68% versus PFS-Ld 57% in the ELOQUENT-2 study and in combination with Pomalidomide/ Dexamethasone with PFS-EPd 10.25 months versus a PFS-Pd 4.67 months in the ELOQUENT-3 study, both in patients with multiple myeloma. In addition to those agents, another mAb, isatuximab, was recently approved based on the results of the ICARIA study.
Conclusions: Monoclonal antibodies are the therapeutic choice of the present and future for multiple myeloma, and research on new monoclonal antibodies is in process. New molecules are expected to be adopted either as monotherapy or as a combination therapy in the near future.
Main subject category:
Multiple myeloma, Monoclonal antibodies, Daratumumab, Elotuzumab
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