Is tandem autotransplantation necessary in myeloma?

Recent availability of novel agents for the treatment of myeloma has resulted in exploration of their use in several different clinical settings.^1,–3  Abdelkefi and colleagues have attempted to replace high-dose melphalan with a modest course of thalidomide (100 mg daily for 6 months). The provocative results of their study raise the question of whether effective maintenance therapy after one transplant obviates the need for tandem transplantation.

However, the study does raise some questions. The 3-year survival of patients in the tandem transplantation arm is similar to that in the Intergroupe Francophone du Myélome (IFM)–96 trial, but significantly inferior to that in the Bologna-96 study.^4,5  However, it is remarkable that the 3-year 88% survival of patients in the single transplantation arm is remarkably better than in the single transplantation arms of the IFM and Bologna studies. Can such differences be attributable solely to thalidomide?

While thalidomide was available as effective salvage therapy for patients relapsing after tandem transplantation, other effective agents such as bortezomib or lenalidomide were not available. How many patients from each arm relapsed, and what their responses were to salvage therapy, is rather difficult to discern from this paper. The fact that 15 of the 18 patients who received thalidomide for relapse died of progressive disease in a relatively short period of time is unusual. In the long-term follow-up of their original observation, Barlogie et al¹  showed almost 50% of patients were alive at 2 years following thalidomide monotherapy. In the era of effective salvage therapy, it is rather unusual to see virtually identical event-free survival and OS in each arm of the study.

This study, although provocative, needs confirmation in a setting where other appropriate salvage therapy options are available to the patients. There are several ongoing clinical trials exploring the role of novel agents in the maintenance setting. Until more data are available, second transplantation should not be abandoned.