Abstract
INTRODUCTION: Autologous stem cell transplantation (ASCT) is the standard of care for younger patients with newly diagnosed multiple myeloma (NDMM). A proportion of patients who underwent this procedure remains in sustained complete response (CR) beyond 10 years from ASCT and are considered operationally cured.
METHODS: We retrospectively analyzed a series of patients with NDMM who underwent ASCT as first line therapy at our institution. To allow a survival beyond 10 years, only those transplanted before December 31st, 2014 were included in the study. Data were updated in January 2025. Baseline characteristics and treatment of long-term survivors were examined. Statistical and survival analysis were performed with STATAv16.1 and RStudio.
RESULTS: From January 1990 to December 2014 238 patients with NDMM underwent ASCT at our institution. Median age was 56 years (IQR, 49-61), and 133 patients (55.0%) were males. ISS risk score showed the expected distribution. Cytogenetic data was available in only 83 patients (34.9%), of whom 14 (16.9%) met high risk cytogenetic criteria.
Chemotherapy was used as induction regimen prior to ASCT in 162 patients (68.1%), while 76 patients (31.9%) received induction with novel agents: 26 (10.9%) received bortezomib-dexamethasone (VD), 22 (9.2%) bortezomib-thalidomide-dexamethasone (VTD), 17 (7.1%) thalidomide-dexamethasone (TD), 5 (2.1%) bortezomib-lenalidomide-dexamethasone (VRD), 3 (1.3%) bortezomib, cyclophosphamide, and dexamethasone (VCD), and 3 (1.3%) other regimens. Overall, 82 patients (34.4%) were included in clinical trials.
The most frequently used conditioning regimen was melphalan 200 mg/m2 (78.1%), followed by melphalan plus total body irradiation (12.2%) and melphalan plus busulphan (8.0%). Additionally, 26 patients (10.9%) underwent a tandem ASCT. Only 83 patients (34.8%) received maintenance therapy, of whom 61 patients (73.5%) received only interferon alone or combined with steroids, 8 (9.6%) thalidomide, 6 (7.2%) thalidomide plus bortezomib, 5 (6.0%) lenalidomide plus dexamethasone, 1 (1.2%) thalidomide plus dexamethasone, 1 (1.2%) ixazomib and 1 (1.2) bortezomib plus dexamethasone.
The CR rate after TASP was 37.0% in the overall series and was significantly higher in patients receiving novel agents-based induction compared to those receiving chemotherapy-based induction (52.6% vs. 29.1%, p<0.001).
With a median follow-up of 12.6 years for the alive patients, the median overall survival (OS) and progression free survival (PFS) in the overall series were 94.0 and 34.9 months, respectively. Significant differences in OS (150.2 vs. 74.4 months, p=0.001) and PFS (40.2 vs. 30.0 months, p=0.003) were observed in patients who received novel drugs-based vs. chemotherapy-based induction therapies. Patients who achieved CR after transplantation displayed significantly longer PFS (48.2 vs. 25.2 months, p=0.001) than patients who did not.
In the overall series, 29 patients (12.2%) were alive and with continued CR at 10 years from ASCT and were considered functionally cured. When comparing treatment groups, the 10-years PFS rate was 28.6% in the novel agent induction group vs. 12.3% in the chemotherapy induction group (p<0.001). At 15 years, the PFS rates were 24.4% vs. 9.6%, respectively (p=0.002). Achievement of CR after transplantation was associated with a higher 10-years PFS rate (34.8% vs. 13.8%, p<0.001). Compared to the general population, the relative survival (RS) at 10 years in the overall series was 47%. Notably, in patients considered functionally cured, the RS was comparable to that of the general population. Eight patients died beyond 120 months of follow-up: six were still in CR, four of them died from causes unrelated to myeloma; the other two patients died of myeloma progression.
CONCLUSION: In our experience, 12% of patients with NDMM who received ASCT as first line therapy remains alive and in sustained CR at 10 years after transplant and are considered operationally cured. Induction treatment with novel drugs is associated with a higher rate of post-transplant CR and an increased likelihood of achieving a functional cure. Current regimens incorporating lenalidomide and anti-CD38 monoclonal antibodies will very likely result in a significantly higher cure rate.
