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A. Vidal-Crespo et al.
MCL) and other where exhibits superiority (transformed CD20dim FL). Moreover, daratumumab potentiates the antitumor activity of CHOP and R-CHOP in all three models.
In addition, as demonstrated in MM, it is likely that daratumumab may modulate the activity and frequency of CD38 expressing immune suppressive cell populations present in NHL, an effect not exerted by rituximab, and therefore may offer a superior overall antitumor effect.29 These may be of special relevance in FL and DLBCL where infiltration of diverse T and myeloid subpopulations is specially prominent.48 The immune-compromised mouse models used in this study preclude the analysis of this immune-modulating activity of daratumumab.
In conclusion, our findings warrant further clinical development of daratumumab in NHL providing a strong rationale for examining its clinical efficacy in different sce- narios, including maintenance therapy after induction therapy, cases with anti-CD20 resistance, FL histologic transformation, and as frontline in combination with the standard of care (CHOP/ R-CHOP).
Acknowledgments
We thank Dr. Adrian Wiestner for his support with this study and his critical revision of the manuscript. Jocabed Roldan, Laura Jiménez, Sandra Cabezas and Ariadna Giro for their technical assistance. The authors would like to thank Dr J Rouquette and Ms L Teyssedre (Imaging facility, ITAV, Toulouse) for performing Daratumumab imaging within the 3D lymphoma cultures by SPIM, and Dr JJ Fournié (CRCT, Toulouse) for article comments.
Funding
This work was carried out at the Esther Koplowitz Center, Barcelona. Genmab and Janssen pharmaceuticals funded this research. Additional grants that contributed to this work included: Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa” for SAF2011/29326 and SAF2014/57708R to PP-G, SAF2015/31242R and SAF2015-31242-R to DC, CIBERONC (CB16/12/00334 and CB16/12/00225), the Integrated Excellence Grant from the Instituto de Salud Carlos III (ISCIII) PIE1313/00033 to EC and PP-G, and finally Generalitat de Catalunya support for AGAUR 2017SGR1009 to DC.
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