Researchers from Italy have reported that newly diagnosed patients with multiple myeloma have improved responses and relapse-free and event-free survivals following double autologous transplants compared to a single autologous transplant, but there was no improvement in overall survival. The details of this study were published in the June 10, 2007 issue of the Journal of Clinical Oncology.

Many transplant centers are treating patients with multiple myeloma with two sequential transplants. There is evidence that this prolongs the time to disease recurrence, but there is little evidence that this approach improves survival, especially if a second transplant is carried out at the time of disease progression. A previous French randomized trial reported that double autologous transplantation improved overall survival among patients with myeloma who did not have at least a very good partial response after one transplant. This has led, in some centers, to the practice of restricting a second elective transplant to those who fail to achieve a CR or near CR following a first transplant. Other centers routinely administer a second transplant only at the time of disease progression following the first transplant. In addition to transplants, there has been a marked increase in the number of active drugs for the treatment of multiple myeloma. Thus, the optimal initial therapy of newly diagnosed patients with multiple myeloma is still evolving.

The current Italian study treated all patients with vincristine, adriamycin and dexamethasone (VAD) and mobilized peripheral blood stem cells with cyclophosphamide and Neupogen® followed by melphalan 200 mg/m2 with stem cell infusion. Patients were aged 60 years or younger. Upon recovery, patients were randomly allocated to receive a second transplant with busulfan and melphalan (n-158) within 3-6 months or no transplant (n=163). Patients in both arms of the study received alfa interferon maintenance. 80-85% of patients received a first transplant and 65% of those randomly allocated to a second transplant actually received the assigned treatment. Data is presented on an intent-to-treat basis with a median follow-up of 55 months.

Table 1: Single Transplants vs. Double Transplants in Multiple Myeloma

One third of the patients allocated to one transplant received an autologous transplant after disease progression. Ten percent of patients receiving two transplants received a third transplant. Fifty percent of patients in both arms were treated with thalidomide or bortezomib as salvage therapy. As in the French study, the primary beneficiaries of a second transplant were those with less than a very good partial response to the first transplant. Patients who had a CR or near CR after the first transplant did not have  improved outcomes. There was a trend for improvement in overall survival (p=10) in patients not achieving a near CR to the first transplant and receiving a second transplant.

Comments: This study confirms the results of the French trials showing that a second transplant benefits primarily those who are not in at least a near CR after the first transplant. This indicates that patients who achieve a CR with the first transplant can delay the second transplant. This study also points out the power of new drugs to prolong survival after progression following an autologous transplant.

Reference: Cavo M, Tosi P, Zamagni E, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 Clinical Study. Journal of Clinical Oncology. 2007; 25:2434-2441.

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Study Confirms Effectiveness of Double Autografts in Multiple Myeloma (12/17/2004)

Thalidomide is Effective Maintenance after Double Autografts for Multiple Myeloma (12/15/2004)

Thalidomide is Effective Maintenance after Double Autografts for Multiple Myeloma (12/15/2004)

Double Autograft Improves Survival of Patients with Multiple Myeloma (12/11/2002)