Anti-Thymocyte Globulin Induces Higher Response Rates and Less Graft-Versus-Host Disease in Multiple Myeloma Patients Undergoing Allogeneic Stem Cell Transplantation.

Abstract

Preclinical experiments have shown a strong anti-myeloma effect of polyclonal anti-thymo-cyte globulin (ATG). We evaluated ATG effect in a melphalan/fludarabine-based conditioning regimen in 138 multiple myeloma (MM) patients who underwent allogeneic stem cell transplantation with (n=79) or without (n=59) ATG. More patients in the group without ATG had experienced relapse to prior auto-transplant (63% vs. 47%, p = 0.08). Patient characteristics were otherwise well matched in both groups. A median ATG dose of 30 mg/kg BW (range, 10-90 mg/kg BW) was administered on days −3 to −1. GvHD prophylaxis was performed with cyclosporine A and short-course methotrexate. Overall response (93% vs. 78%, p=0.03) and complete response (59% vs. 39%, p=0.04) at day 100 were higher in the patients treated with ATG than in those without ATG. ATG led to a lower incidence of severe grade III/IV acute GvHD (11% vs. 22%, p=0.10), and chronic GvHD (23% vs. 65%, p<0.001). The rate of complete remissions increased in patients who had received the higher ATG dose: 57% in those who received ATG ≤ 30 mg/kg BW, vs. 63% in those who received ATG > 30 mg/kg BW. The rate of OR increased from 78% in the no-ATG group to 91% in patients who received ATG ≤ 30 mg/kg BW, and to 96% in patients who received ATG > 30 mg/kg BW (p=0.02). Separate analysis of patients transplanted from a sibling donor also showed a trend to better OR (86% vs. 78%) and CR (55% vs. 39%) for patients who received ATG (all patients received ATG at a dose ≤ 30 mg/kg) compared to the non-ATG group, however due to low numbers this difference did not reach statistical significance. Though the non-ATG group contained more patients who had relapsed to prior autografting, this as has been reported before, would not influence response rates. In the multivariate analysis of prognostic factors for achievement of a CR, ATG was the only significant prognostic factor (RR: 2.57; 95% CI: 1.17-5.64; P=0.02). The estimated overall survival (OS) at three years was 53% (95% CI: 40-66%) for the ATG group (p=0.46), and 43% (95% CI: 29-57%) for the non-ATG group (p=0.46), while progression-free survival (PFS) at three years was 39% (95% CI: 27-51%) for the ATG group, and 27% (95% CI: 14-40%), for the non-ATG group (p=0.55). The current results suggest a dose dependent beneficial effect of ATG in terms of myeloma cytotoxicity as well reduction of the incidence of chronic GvHD.