Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial

Background Postsurgical recurrence of hepatocellular carcinoma (HCC) is fre quent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence . Methods Between 1992 and 1995, we did a randomised trial in which 150 patie nts who had undergone curative resection for HCC were assigned adoptive imm unotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes a ctivated vitro with recombinant interleukin-2 and antibody to CD3 were infu sed five times during the first 6 months. Primary endpoints were time to fi rst recurrence and recurrence-free survival and analyses were by intention to treat. Findings 76 patients received 370 (97%) of 380 scheduled lymphocyte infusio ns (mean cell number per patient 7.1x10(10) [SD 2.1]; CD3 and HLA-DR ceils 78% [16]), and none had grade 3 or 4 adverse events. After a median follow- up of 4.4 years (range 0.2-6.7), adoptive immunotherapy decreased the frequ ency of recurrence by 18% compared with controls (45% [59] vs 57% [77]) and reduced the risk of recurrence by 41% (95% CI 12-60, p=0.01). Time to firs t recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37-59] vs 33% [22-43] at 3 years, 38% [22-54] vs 22% [11-34] at 5 years; p=0.008). The immunotherapy group had significantl y longer recurrence-free survival (p=0.01) and disease-specific survival (p =0.04) than the control group. Overall survival did not differ significantl y between groups (p=0.09). Interpretation Adoptive immunotherapy is a safe, feasible treatment that ca n lower recurrence and improve recurrence-free outcomes after surgery for H CC.