In our single center experience of 41 patients, salvage auto-SCT appears to be a safe and effective treatment for relapsed multiple myeloma. The overall response rate of 55% in assessable patients and low rate of treatment-related mortality suggest a favorable risk/benefit profile.
After a median follow-up of 15 months, the median PFS for all patients after salvage auto-SCT was 8.5 months. Other studies have reported higher estimates,7,8,10,12
but in the setting of salvage auto-SCT at the time of first relapse10,12
or with no data provided on the number of prior therapies.7,8
Our data suggest that receipt of multiple prior lines of therapy is a strong prognostic factor for poor outcomes, which would explain the more durable responses seen when salvage auto-SCT is used in patients without significant pre-treatment. In a recent small study describing patients with a greater degree of pre-treatment than our patient cohort (median six prior therapies versus median three, respectively), the median PFS was 6.8 months.11
The number of prior lines of therapy (≥5 vs <5) was the strongest predictor in multivariate models of both PFS and OS after salvage auto-SCT. This is likely a surrogate marker for the presence of chemoresistant disease or the persistence of residual toxicities from prior therapies. It can be noted that the presence of cytogenetic abnormalities at any time prior to salvage transplant was not predictive of either PFS or OS, and neither was the presence of responsive disease prior to transplant. Our study is the first to investigate the significance of the number of prior lines of therapy as a prognostic factor in salvage auto-SCT for myeloma, and this bears confirmation in additional series from other centers.
Time to progression after initial transplant was also independently predictive of OS, which is consistent with other previous reports of salvage auto-SCT.7,9,10,12,15
Some studies have found that the interval between transplants is prognostic of OS.11,13,14
This factor is likely a suboptimal surrogate for TTP after initial transplant, which in our study was not significantly associated with either PFS or OS in univariate or multivariate analyses. TTP ≤12 months after initial auto-SCT has also been shown to be predictive of shorter OS in a large group of patients with myeloma, suggesting that this factor is highly prognostic irrespective of subsequent therapies given at relapse.17
A number of conditioning regimens were used for the salvage auto-SCT in our cohort: melphalan 200 mg/m2, reduced dose melphalan and TBI-based regimens were each used in 25–35% of patients in this cohort. (Only three patients received BU/CY.) The choice of conditioning regimen was made by the treating physician and was based in large part on age, comorbid disease, prior therapy and renal function. There was no difference in PFS or OS between patients who received reduced dose melphalan, full-dose melphalan or TBI-based conditioning, suggesting that salvage autologous transplant may still be effective in the setting of renal insufficiency or other comorbidities.
The limitations of this study include its retrospective nature, limited sample size and incomplete data on known prognostic factors such as β-2 microglobulin and cytogenetics. In the context of the available literature on salvage auto-SCT for multiple myeloma, however, this study does support the safety of salvage auto-SCT and confirms the importance of TTP after initial transplant as a prognostic factor.
The value of tandem transplantation when compared to single auto-SCT is controversial. Although a number of studies have shown improved PFS and OS after tandem transplantation, one recent study suggested superior outcome after single auto-SCT with thalidomide maintenance. 18
The results of that study are difficult to interpret, as has been discussed.5
The relative merits of salvage auto- SCT at relapse, as compared with an upfront tandem transplant, are unknown. Preliminary results from a randomized trial of these two approaches show no difference in OS; however, longer follow-up is needed.10
For patients who have already received a single auto-SCT, our data indicate that salvage auto-SCT is safe and may be reasonably effective.
We conclude that second salvage auto-SCT generally has a favorable risk/benefit profile in patients with relapsed multiple myeloma. Patients with two adverse prognostic factors (≥5 prior lines of therapy and a TTP after initial transplant of ≤12 months) are unlikely to benefit significantly. Salvage auto-SCT should therefore be considered for appropriate patients with relapsed multiple myeloma.