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Impact of lenalidomide on immune functions in the setting of maintenance therapy for multiple myeloma

Leukemia volume 29, pages 2098–2100 (2015)Cite this article

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Lenalidomide is an effective and widely used therapeutic agent for multiple myeloma (MM). The combination of its anti-neoplastic effect on myeloma cells1, 2 and immunomodulatory properties3, 4 makes lenalidomide a major therapeutic drug in the treatment algorithms for MM patients. This is supported by its ability to confer a positive impact on outcome in the setting of maintenance therapy in young MM patients receiving autologous stem cell transplantation.5, 6, 7 An important area of lenalidomide investigation is the study of both its reversible effects on myeloma-mediated immune suppression and its positive effects on antitumor immunity. Previous studies have demonstrated that lenalidomide promotes T-cell proliferation and suppresses inhibitory factors such as program death receptor 1, in addition to enhancing T-8 and NK-cell function.9 However, its immune effects in MM patients treated with lenalidomide alone remain to be elucidated. This pilot prospective study aimed to assess T-cell polarization and the cytokine secretion profile in patients receiving lenalidomide in the maintenance setting (MM-Len group) compared with patients treated for MM without any maintenance (MM group) and to healthy donors (HD group).

Ten patients belonged to the MM-Len group. Their median age was 60.3 years (49.1–64.4) and, at the time of analysis, they had received between 4 and 12 cycles of lenalidomide alone (one cycle=28 days) at a dose ranging between 5 and 15 mg/day. Five of them had previously received 3 cycles of RVD (lenalidomide, bortezomib and dexamethasone), autologous stem cell transplant (ASCT), conditioning by melphalan, then consolidation by 3 cycles of RVD, followed by maintenance therapy with continuous oral lenalidomide alone. The other five patients received induction with the RVD combination, then maintenance with lenalidomide. Seven patients were in very good partial response (VGPR) and three in complete response (CR) at the time of analysis. The MM group included eight patients after ASCT without any maintenance at the time of analysis (Supplementary Table S1). The two groups were comparable in terms of age, sex, interval between diagnosis and time of analysis, and disease status (data not shown). All patients treated for MM were in CR or VGPR at the inclusion in the study. The HD group comprised six healthy donors.

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Acknowledgements

MM would like to thank Pr J.V. de Melo (Adelaide, Australia) for critical reading of the manuscript. We acknowledge the technical and logistical support of V Dehame. EB was supported by educational grants from the ‘Association for Training, Education and Research in Hematology, Immunology and Transplantation’ (ATERHIT) and by Fulbright Foundation. We also thank the ‘Région Pays de Loire’, the ‘Association pour la Recherche sur le Cancer (ARC; grant #3175 to MM and BG)’, the ‘Fondation de France’, the ‘Fondation contre la Leucémie’, the ‘Agence de Biomédecine’, the ‘Association CentpourSang la Vie’, the ‘Association Laurette Fuguain’, the IRGHET and the ‘Ligue Contre le Cancer’ (Comités Grand-Ouest) for their generous and continuous support of our clinical and basic research work. Our transplant programs are supported by several grants from the French National Cancer Institute (PHRC, INCa to MM).

Author contributions

EB and MM designed and performed research, analyzed and interpreted the data, and wrote the manuscript. EB and AC performed research. NB, VR, TG, VD, BM, TG, SLG and PM provided biological samples. EB, BG and MM interpreted the data.

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Authors and Affiliations

  1. Université Pierre et Marie Curie, Paris, France

    E Brissot & M Mohty

  2. INSERM UMRs 938, Paris, France

    E Brissot & M Mohty

  3. Hématologie Clinique, CHU Hôtel-Dieu, Nantes, France

    E Brissot, A Clavert, N Blin, V Roland, T Guillaume, V Dubruille, B Mahe, T Gastinne, S Le Gouill, P Moreau & M Mohty

  4. CRCNA, UMR 892 INSERM- 6299 CNRS, Nantes, France

    E Brissot, T Guillaume, S Le Gouill & M Mohty

  5. INSERM UMR 1098, Besançon, France

    B Gaugler

  6. Université de Franche-Comté, Besançon, France

    B Gaugler

  7. EFS Bourgogne Franche-Comté, Besançon, France

    B Gaugler

  8. Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France

    M Mohty

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  1. E Brissot
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Correspondence to M Mohty.

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Competing interests

MM, PM and SLG have received research support and lecture fees for work outside of the current study from Celgene and Janssen, whose product is discussed in this article. The remaining authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Brissot, E., Clavert, A., Blin, N. et al. Impact of lenalidomide on immune functions in the setting of maintenance therapy for multiple myeloma. Leukemia 29, 2098–2100 (2015). https://doi.org/10.1038/leu.2015.64

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