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Combining allogeneic immunotherapy with an mTOR inhibitor for advanced renal cell carcinoma

Bone Marrow Transplantation volume 45, pages 1360–1362 (2010)Cite this article

Advanced renal cell carcinoma (RCC) is responsive to a graft-vs-tumor (GVT) effect following reduced-intensity conditioning (RIC) and allogeneic hematopoietic stem cell transplantation (HCT).1, 2 However, enthusiasm for the approach has been tempered by the low rate of complete responders and treatment-related toxicities that include graft-vs-host disease and infectious complications. In their recent report, Bregni and co-workers observed a 5-year survival rate of 20% for 25 patients with metastatic RCC treated by RIC and allogeneic HCT from HLA-compatible sibling donors. Of interest, three long-term survivors had stable metastatic disease and had received post transplant vascular endothelial growth factor (VEGF) receptor-targeted tyrosine kinase inhibitors including sunitinib or sorafenib.3 The authors further speculate on the potential for clinical benefit by combining allogeneic HCT with novel targeted therapies for metastatic RCC.

Retrospective analyses of RCC patients treated by RIC and allogeneic HCT have suggested that RCC patients from favorable or intermediate risk groups defined by the Memorial Sloan-Kettering Cancer Center prognostic criteria and with clear-cell tumors have achieved better outcomes.2, 3 However, RCC patients with these clinical features are most likely to receive initial treatment with VEGF-targeted therapies including sunitinib or bevacizumab plus IFN-α based on the results of phase III clinical studies.4, 5 The optimal salvage strategy for patients failing VEGF-directed therapies remains unclear. Inhibitors of the mammalian target of rapamycin kinase (mTOR inhibitors) including temsirolimus, everolimus and rapamycin have clinical activity against RCC as monotherapy. For patients with clear-cell RCC receiving second-line everolimus after failing a VEGF-directed therapy, the magnitude of clinical benefit was modest, with an objective response rate of only 1% and a median PFS of 4.0 months.6 Thus, the potential for combining mTOR inhibitors with other therapies is of significant interest.

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Acknowledgements

This research was supported in part by National Institutes of Health Grants CA121912 (SST) and CA106512 (EHW).

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  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    S S Tykodi, L N Voong & E H Warren

  2. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

    S S Tykodi & E H Warren

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  1. S S Tykodi
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Correspondence to E H Warren.

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Tykodi, S., Voong, L. & Warren, E. Combining allogeneic immunotherapy with an mTOR inhibitor for advanced renal cell carcinoma. Bone Marrow Transplant 45, 1360–1362 (2010). https://doi.org/10.1038/bmt.2009.338

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