Research Papers:

Phase I dose-escalation study of F50067, a humanized anti-CXCR4 monoclonal antibody alone and in combination with lenalidomide and low-dose dexamethasone, in relapsed or refractory multiple myeloma

Guillemette Fouquet, Stéphanie Guidez, Valentine Richez, Anne-Marie Stoppa, Christophe Le Tourneau, Margaret Macro, Cécile Gruchet, Arthur Bobin, Niels Moya, Thomas Systchenko, Florence Sabirou, Anthony Levy, Paul Franques, Hélène Gardeney, Lionel Karlin, Lotfi Benboubker, Monia Ouali, Jean-Claude Vedovato, Pierre Ferre, Mariya Pavlyuk, Michel Attal, Thierry Facon and Xavier Leleu _

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Oncotarget. 2018; 9:23890-23899. https://doi.org/10.18632/oncotarget.25156

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Guillemette Fouquet1,*, Stéphanie Guidez2,11,*, Valentine Richez2, Anne-Marie Stoppa3, Christophe Le Tourneau4, Margaret Macro5, Cécile Gruchet2, Arthur Bobin2, Niels Moya2, Thomas Syshenko2, Florence Sabirou2, Anthony Levy2, Paul Franques2, Hélène Gardeney2, Lionel Karlin6, Lotfi Benboubker7, Monia Ouali10, Jean-Claude Vedovato10, Pierre Ferre10, Mariya Pavlyuk10, Michel Attal8, Thierry Facon9 and Xavier Leleu2,11

1Institut Imagine, Unité Inserm U1163, Centre National de la Recherche Scientifique CNRS ERL8254, Paris, France

2Hôpital La Milétrie, Centre Hospitalier Universitaire, Poitiers, France

3Institut Paoli Calmettes, Marseille, France

4Institut Curie, Paris, France

5Centre Hospitalier Universitaire, Caen, France

6Centre Hospitalier Lyon Sud, Lyon, France

7Centre Hospitalier Universitaire Tours, Tours, France

8Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France

9Service des Maladies du Sang, Centre Hospitalier Régional Universitaire, Lille, France

10Institut de Recherche Pierre Fabre, Toulouse, France

11Inserm Centre d’Investigation Clinique U1402, Centre Hospitalier Universitaire, Poitiers, France

*Co-first author

Correspondence to:

Xavier Leleu, email: xavier.leleu@chu-poitiers.fr

Keywords: multiple myeloma; CXCR4; monoclonal antibody; immunotherapy; homing of tumor cells

Received: January 08, 2018     Accepted: March 29, 2018     Published: May 08, 2018


Purpose: Multiple myeloma (MM) remains an incurable disease as tumor cells ultimately resist to all available drugs. Homing of tumor cells to the bone marrow microenvironment, involving especially the CXCR4/SDF-1 axis, allows them to survive, proliferate and resist to therapy. F50067, a humanized anti-CXCR4 IgG1 antibody, has promising preclinical activity in MM.

We present a phase I multicenter escalation study in relapsed/refractory MM (RRMM) to determine the maximum tolerated dose (MTD) for F50067 alone and in combination with lenalidomide and low dose dexamethasone (Len-Dex).

Experimental design: 14 end-stage RRMM patients received F50067 single agent (n = 10) or in combination with Len-Dex (n = 4).

Results: One dose-limiting toxicity was observed, a grade 4 neutropenia lasting more than 7 days in combination arm. MTD could not be established. Thrombocytopenia was observed in 100% and neutropenia in 92.9% of patients with no cases of febrile neutropenia and no severe bleeding or hematoma. Non-hematological adverse events were of mild to moderate severity.

Nine patients (6 in single arm and 3 in combination arm) were evaluable for response, with 66.7% overall response rate (≥PR) in combination arm, and 33.3% of disease control (≥SD) in single agent arm. At the time of study termination, 55.6% had progressed.

Conclusion: This study suggests that egression of tumor cells to the blood stream can represent a novel therapeutic strategy for MM. However, because of significant hematological toxicity, this study had to be discontinued. Further studies are needed to validate the feasibility of this approach in clinical practice.

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