1.
In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT
Beksac, M., Eikema, D. J., Koster, L., Hulin, C., Poiré, X., Hamladji, R. M., Gromek, T., Bazarbachi, A., Ozkurt, Z. N., Pabst, T., et al
Bone marrow transplantation. 2024
Abstract
Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27-2.25, p < 0.001) and OS (HR:1.46 (1.14-1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33-1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18-1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25-1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study.
2.
Busulfan/Cyclophosphamide Compared with Melphalan as a Conditioning Regimen for Autologous Transplantation of Multiple Myeloma: A Long-Term Assessment
Zhou, S., Zhai, Y., Yan, L., Shi, X., Shang, J., Wu, D., Fu, C., Jin, S.
Journal of clinical medicine. 2023;12(19)
Abstract
BACKGROUND Melphalan was poorly available in mainland China. The aim of this study is to explore the dose-adjusted busulfan/cyclophosphamide (BU/CY) as an alternative regimen in auto stem cell transplantation (ASCT) for multiple myeloma (MM). METHODS A total of 105 newly diagnosed MM patients undergoing ASCT during May 2012 and August 2017 were retrospectively analyzed. The BU/CY regimen was applied to 64 patients. Busulfan (9.6 mg/kg or 8.0 mg/kg in total) and cyclophosphamide (3.6 g/m(2) or 3.0 g/m(2) in total) were administered according to the creatinine clearance rate (CCR). A high-dose melphalan (HDMEL) regimen (200 mg/m(2)) was given to the other 41 patients. RESULTS At a median follow-up of 65 (1~119) months, estimated overall survival (OS) and progression-free survival (PFS) at 104 months in the BU/CY and HDMEL groups were 35.6% vs. 20.5% (p = 0.263) and 20.2% vs. 2.4% (p = 0.035), respectively. The median overall survival (OS) and PFS of the HDMEL and BU/CY groups were 55 vs. 70.5 months and 26 vs. 46.5 months, respectively. In multivariate analysis, the BU/CY regimen was found to be the only protective factor for PFS. No lethal toxicity was found in the BU/CY group, and treatment-related mortality (TRM) in 100 days was similar to the HDMEL group. CONCLUSIONS MM patients may also benefit from the dose-adjusted BU/CY regimen.
3.
Autologous stem cell transplantation in multiple myeloma patients with renal impairment
Zhai, Y., Yan, L., Jin, S., Yan, S., Yao, W., Shang, J., Shi, X., Wang, R., Kang, H., Lu, J., et al
Annals of hematology. 2023
Abstract
Renal impairment (RI) used to exclude multiple myeloma (MM) patients from autologous stem cell transplantation (ASCT) for safety concerns. Here, we retrospectively reviewed 34 consecutively transplanted patients with creatinine clearance < 60 ml/min at ASCT in recent 5 years at our institution. Busulfan/cyclophosphamide and high-dose melphalan were both employed as conditioning regimens. We found 62% grade 1-2 oral mucositis, 12% grade 3 oral mucositis, 48% grade 3 infection, 8% grade ≥ 4 infection, 50% grade 1 transient creatinine increase, 15% cardiac adverse events, and 12% engraftment syndrome. One case of secondary platelet graft failure and 1 case of transplantation-related mortality were observed. Interleukin-6 concentration was elevated among patients with increased body temperature and/or N-terminal pro-brain natriuretic peptide during engraftment, and close monitoring of these markers may help to predict susceptibility to cardiac events and engraftment syndrome. Adverse events occurred frequently, but the majority were manageable in this cohort. ASCT would further deepen the anti-myeloma efficacy and slightly ameliorated renal function. With a median follow-up of 26.2 months post transplantation (range: 1.6-74.8 months), the median progression-free survival (PFS) and overall survival (OS) post-transplantation of patients undergoing first-line transplantation were not reached; the median PFS post-transplantation of patients undergoing rescue transplantation was 19.2 months and the median OS was not reached.