The addition of total body irradiation to nonmyeloablative chemotherapy prior to adoptive cell transfer does not provide any response or survival benefits but increases the risk of developing thrombotic microangiopathy (TMA), investigators reported.
Sequential clinical studies in the Surgery Branch of the National Cancer Institute had suggested that adding total body irradiation (TBI) to the preparative regimen for adoptive cell transfer could increase the complete response rate.
To evaluate in a randomized trial whether the addition of TBI to the nonmyeloablating (NMA) chemotherapy preparative regimen did indeed increase the complete response rate, 101 patients with metastatic melanoma with at least two measurable lesions were randomly assigned to receive only NMA chemotherapy or NMA chemotherapy and TBI. Patients in both treatment groups then underwent adoptive cell transfer and received intravenous infusions of tumor-infiltrating lymphocytes and high-dose IL-2. Only patients who received both NMA chemotherapy and TBI received CD34+ hematopoietic stem cells.
Complete response (CR) rate was 24% in both experimental arms (NMA: 12 of 51 patients, 95% CI 13% to 37%; NMA and TBI: 12 of 50 patients, 95% CI 13% to 38%). Progression-free survival and overall survival were similarly identical for the two experimental groups, Dr. Stephanie Goff of the National Cancer Institute and her associates reported (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2016.66.7220).
The NMA plus TBI group had a high incidence of late-onset TMA (27%), complications that led to one treatment-related death.
“Addition of TBI did not increase CR rates or impact overall survival, but did introduce a new toxicity in the form of TMA. The nonmyeloablative chemotherapy regimen thus seemed to provide sufficient lymphodepletion for successful adoptive transfer without the need to add TBI,” Dr. Goff and associates concluded.
The Center for Cancer Research at the National Cancer Institute, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Lion Biotechnologies funded the study. Four investigators disclosed financial ties with various companies. The other investigators had no disclosures to report.
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