Side effects of CXC-chemokine receptor 4 - directed Endoradiotherapy with Pentixather prior to Hematopoietic Stem Cell Transplantation

Maurer, S., Herhaus, P., Lippenmeyer, R., Hänscheid, H., Kircher, M., Schirbel, A., Maurer, H.C., Buck, A.K., Wester, H.J., Einsele, H., Grigoleit, G.U., Keller, U., Lapa C. (2019). J Nucl Med 60, 1339-1405.

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The chemokine receptor CXCR4 is a transmembrane receptor involved in survival, proliferation and dissemination of different cancers, including hematopoietic malignancies. Relapsed/refractory hematopoietic cancers are frequently resistant to conventional therapy and novel highly active strategies are urgently needed. CXCR4-directed endoradiotherapy constitutes a highly promising targeted therapeutic concept. Here we investigated the adverse effects of this novel treatment approach. Methods: Twenty-two patients with heavily pretreated lymphoproliferative or myeloid malignancies were treated with 177Lu- or 90Y-Pentixather - a CXCR4-directed therapeutic radioligand - prior to conventional conditioning therapy followed by autologous or allogeneic hematopoietic stem cell transplantation. Twenty-five CXCR4-directed endoradiotherapies were conducted in those patients. Adverse events occurring between endoradiotherapy and the start of conventional conditioning therapy were retrospectively analyzed and graded for the estimation of the safety profile. Results: CXCR4-directed endoradiotherapy with Pentixather showed a favorable toxicity profile. As expected the hematopoietic system was most affected with all subjects developing cytopenias. Except one acute kidney failure grade 3 due to tumor lysis syndrome, overall nephro- and hepatotoxicity was low. Other higher grade adverse events were either transient and resolved, or easily manageable. Conclusion: Therapy with radiolabeled Pentixather appears to be well tolerated and easily applicable when proceeding conventional conditioning regimens for hematopoietic stem cell transplantation.