CALGB 90003: Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: An Intergroup Phase II Study.

A graft-versus-tumor effect mediated by non-myeloablative allogeneic stem cell transplantation has been reported for patients with cytokine-refractory, metastatic renal cell carcinoma (RCC). An Intergroup phase II trial was undertaken to further define the feasibility, toxicity and efficacy of this approach in a multi-institutional setting. The conditioning regimen was fludarabine 30mg/m²/d, days −7 to −3, and cyclophosphamide 60mg/kg/d, −4 and −3. Patients received 2 to 8 x 10⁶ G-CSF-mobilized CD34+ cells/kg from a 6/6 HLA-matched sibling donor. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus (target level 5–10 ng/ml) starting day −1 and methotrexate 5 mg/m² days +1, +3, +6. Tacrolimus was tapered to zero between days +60 and +90. Twenty-two patients were enrolled at 14 different institutions. Patient characteristics included median age of 53, (range, 39–60) and a performance status of 0 in 14 patients and 1 in 8 patients. Prior systemic therapies included 1 regimen in 13 patients, 2 regimens in 5 patients and 3 regimens in 1 patient. One patient failed to engraft and had autologous recovery. Greater than 95% donor T cell chimerism was seen in 10 of 13 patients (77%) by 120 days after BMT. The day 100 regimen-related mortality was 0 of 22 (0%). Acute GVHD was observed in 7 patients (41%). Chronic GVHD was observed in 11 patients (65%) with one patient death from liver failure secondary to chronic GVHD. Eleven patients have died: 7 from disease progression; 1, renal failure (not treatment related); 1, sepsis (pseudomonas); 1, liver failure secondary to chronic GVHD (treatment related); 1, unknown. No objective response has been reported in the 17 patients with follow-up data available. Progressive disease was reported for 14 patients. Median progression-free survival is 4.1 months (95% C.I.: 3.9 – 4.4 months). Median overall survival is 5.6 months (95% C.I.: 4.3 – 12.3 months). Non-myeloablative allogeneic stem cell transplant for metastatic RCC is feasible in a multi-institutional setting. Significant morbidity limits the eligible patient population. Lack of anti-tumor effect highlights the need for stringent patient selection and for further manipulation of the current approach. Non-myeloablative allogeneic stem cell transplantation in metastatic RCC remains investigational.