Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: A CALGB Intergroup Phase II Study

• Published in: Biology of blood and marrow transplantation 2006-07, Vol.12 (7), p.778-785
• Main Authors: Rini, Brian I., Halabi, Susan, Barrier, Robert, Margolin, Kim A., Avigan, David, Logan, Theodore, Stadler, Walter M., McCarthy, Philip L., Linker, Charles A., Small, Eric J.
• Format: Article
• Language: English
• Subjects: Adult; Allogeneic; Carcinoma, Renal Cell - secondary; Carcinoma, Renal Cell - therapy; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - mortality; Graft vs Tumor Effect - immunology; Humans; Immunosuppression - methods; Immunotherapy, Adoptive - methods; Kidney Neoplasms; Male; Middle Aged; Nonmyeloablative transplant; Renal cell carcinoma; Stem Cell Transplantation - methods; Survival Analysis
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2006.03.011

A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT. The conditioning regimen was fludarabine 30 mg · m −2 · d −1 on day (d) −7 through d −3 and cyclophosphamide 60 mg · kg −1 · d −1 on d −4 and d −3. Patients received 2-8 × 10 6 CD34 + cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120. No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach. Allogeneic SCT remains investigational in RCC.