The role of tandem and salvage autologous stem cell transplant (ASCT) in multiple myeloma (MM) has been a subject of interest for many myeloma investigators. Further, the role of tandem ASCT in patients achieving very good partial remission (VGPR) or complete remission (CR) has not been studied prospectively.
We conducted a prospective phase II clinical trial in which enrolled MM patients are assessed after the first ASCT. Patients achieving ≤ partial remission (PR) were offered 2nd tandem ASCT followed by maintenance therapy. Patients that were found to be ≥VGPR were offered maintenance therapy followed by salvage ASCT at the time of relapse.
Busulfan 0.75 mg/kg PO q 6 hr days -8 through -5, Cyclophosphamide (Cy) 60 mg/kg IV days -3 and -2, and Etoposide 10 mg/kg IV days -4 to -2 were used as the conditioning regimen for the first ASCT. Patients receiving a second ASCT received 96-hour (days -6 to -3) continuous IV Cy 6 gr/m2 and low dose total body irradiation (loTBI) 600 cGy (days -2 and -1). Etoposide was omitted if patients were ≥65 years. Melphalan 140 mg/m2 was used in lieu of TBI if prior irradiation did not allow for TBI.
Between the years 2001–2009, 76 patients were enrolled into the study. 54 patients achieved ≥VGPR. 31 patients had ≤ PR and were offered ASCT. Of these patients, 21 patients ultimately received tandem ASCT and 1 patient had tandem autologous-allogeneic transplants. Reasons for not receiving the planned tandem ASCT were lack of socioeconomic resources, physical co-morbidities, and patient refusal. There were no treatment related mortalities in the ASCT patients.
Progression-free (PFS) and overall (OS) were compared between the single ASCT (n=54) and tandem ASCT (n=21) groups. The median PFS for the single ASCT group was 27 months (range, 3–107) and 21 months (range, 7–101) in the tandem group (P=0.814). OS was 76 months (range, 5–144) vs. 38 months (range, 12–128), respectively (P=0.121). At the time of submission, a total of 26 (48%) patients in the single ASCT group and 6 (30%) patients in the tandem group are still alive.
Among the tandem patients, 2 later underwent salvage ASCT and 3 went on to receive non-myeloablative allogeneic transplants. In the single ASCT group, 6 had salvage ASCT and 7 had allogeneic SCT. All salvage transplants were done at a median of 30 months (range, 8–90) from the last ASCT.
Patients who declined tandem transplant had a median PFS of 20 months (range 4–38). Patients who did not quality for tandem ASCT had a median PFS of 28 months (range 3–107) (p–0.08). Median OS between the two groups was 53 months (range 5–95) and 57.5 months (12–144), respectively (p–0.67).
Patients who achieve ≥VGPR after 1st ASCT have similar PFS and a trend toward better OS than patients who had tandem ASCT. Thus, the use of such response criteria may identify a group of lower risk patients that will do well without upfront tandem ASCT.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.