Benefit and timing of second transplantations in multiple myeloma: clinical findings and methodological limitations in a European Group for Blood and Marrow Transplantation registry study

Purpose: To use European Group for Blood and Marrow Transplantation registry data to assess the benefit and optimal timing of a double-autologous transplantation strategy for patients with myeloma. Patients and methods: 7,452 transplantation patients described as being either in a multiple graft program ("planned") or not, were analyzed on an intention-to-treat basis. Subsequent multivariate analyses concentrated on the real occurrence of second transplantation, survival, relapse, and transplant-related mortality. Results: Although the transplantation rate in the planned group failed to reach 60%, the median survival from transplantation is 60 months for the planned, compared with 51 months for the remainder group. While the hazard ratio of the planned group is 0.89 (95% CI, 0.79 to 1.00; P =.05) before approximately 70 months, this "effect" is reversed after 70 months, with the hazard ratio estimated as 3.01 (95% CI, 1.07 to 8.46; P =.04). A time-dependent multivariate Cox analysis shows that, taking patients without a second transplantation as a reference group, those receiving a second transplantation in first remission (ie, before relapse) show an increased probability of transplant-related mortality, especially if the transplantation is performed more than 12 months after the first, and the reduction of the risk of relapse is less than when the transplantation is performed earlier. Performing a second transplantation after relapse does not seem to prolong survival, though a second transplantation before relapse is associated with a higher probability of mortality. Conclusion: To improve survival of tandem autologous transplantation in multiple myeloma, the second transplantation should preferably be performed before relapse and within 6 to 12 months of the first transplantation.