Incidence of Malignancy on Tacrolimus Monotherapy Versus Combination Therapy: A Report from the TICTAC Trial

Abstract

Purpose Recent ISHLT Registry reports indicate approximately 20 % of patients will suffer a malignancy within 5 years post-transplant. The propensity towards malignancy is directly associated with immunosuppression, which is typically a combination of a calcineurin inhibitor, cell cycle modifier and steroids. However, patients in the recently reported TICTAC trial were treated with tacrolimus (TAC) monotherapy or TAC / mycophenolate mofetil (MMF) along with universal steroid weaning within the first 8-10 weeks post-transplant. We examined the incidence of malignancy in subjects from the TICTAC trial to assess the risk of malignancy in patients according to immunosuppressive strategy. Methods and Materials As previously described, from 4/04 – 8/08 150 adult heart transplant patients were enrolled and randomized to monotherapy or dual therapy with TAC and MMF. Patients were followed for survival and the occurrence of malignancies long-term. Results The table below shows the occurrence of malignancy post-transplant. The freedom from malignancy was similar between the monotherapy and TAC/MMF groups. Survival was similar between groups regardless of the incidence of cancer. Conclusions TAC monotherapy is likely the minimum immunosuppression feasible in heart transplantation. There was no difference in the incidence of malignancy between groups. These results might reflect the inherent carcinogencity of TAC. Malignancy TAC Monotherapy Group (n=79) TAC / MMF Group (n=71) p-value Pre-transplant history of malignancy 10.1 % (8 pts) 4.2 % (3 pts) 0.16 Any Malignancy post-transplant 30.4 % (20 pts) 23.9 % (17 pts) 0.38 Hematologic malignancy post-txp 3.8% (3 pts) 7.0% (5 pts) 0.38 Skin malignancy post-txp 17.7% (14 pts) 14.1% (10 pts) 0.54 Freedom From Malignancy 1 Year Post Txp 92.2% 97.2% 0.72 Freedom From Malignancy 3 Years Post Txp 85.2 % 91.4% 0.72 Freedom From Malignancy 5 Years Post Txp 76.7% 79.8% 0.72 Survival 7 years Post-Txp: NO MALIGNANCY 78.7 % 91.1% 0.56 Survival 7 yrs Post-Txp: WITH MALIGNANCY 86.1% 75% 0.56