Objectives: Upfront autologous stem cell transplantation (ASCT) remains standard of care for eligible patients with newly-diagnosed multiple myeloma (NDMM). The management and prognosis of ASCT eligible multiple myeloma (MM) has changed and improved with the introduction of novel agents. These data are largely derived from clinical trials and might not reflect real-world patient outcomes accurately,especially in China. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront ASCT between 2007-2023 in China real-world.

Methods: We conducted a single-center retrospective analysis of patients with NDMM who underwent ASCT at the first affiliated hospital of Sun Yat-sen university between 2007 to 2023. Patients were grouped by the year of ASCT: cohort 1: 2007-2012 (n=79), cohort 2: 2013-2018(n=143), cohort 3: 2019-2023 (n=168). High-risk cytogenetic abnormalities were defined as del(17p), t(4;14), t(14;16) and 1q21 amplification by fluorescence in situ hybridization（FISH）. We summarized the dynamic changes in the clinical characteristics, treatment, response rate, collected CD34+ cell dose and survival.

Results: We included 390 MM patients in the analysis. The proportion of patients older than 65 years slightly increased from 5.1% in the 2007-2012 cohort to 10.7% in the 2019-2023 cohort. The prevalence of extramedullary disease increased significantly from 13.9% in the 2007-2012 cohort to 27.4% in the 2019-2023 cohort (P = 0.019). Similarly, secondary amyloidosis was more common in recent years, increasing from 2.5% to 14.3% (P = 0.012). The use of FISH detection increased from 2007 to 2023. The use of tandem ASCT saw a significant increase from 0% in the cohort 1 to 12.5% in the cohort 3 (P < 0.001). In total, all of patients were treated with one or more novel agents. Bortezomib-containing regimens were preferred as initial treatment, they were used in 328 patients (84.1%). Induction regimens evolved from bortezomib and dexamethasone to immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) based triplet and quadruple regimens. And the introduction of Dara-based regimens in the most recent cohort (9.0%) highlights the incorporation of newer therapies into induction regimens. The use of lenalidomide has risen significantly, becoming the dominant maintenance therapy in the 2019-2023 cohort (51.6%). Response rates prior to ASCT steadily increased, with 24.1% and 8.5% achieving a ≥CR and MRD negativity compared to 40.5% and 29.8% between 2007-2012 and 2019-2023. Best response post ASCT improved from 68.4% and 74.4% achieving ≥CR and MRD negativity between 2007-2012 to 82.1% and 80.4% between 2019-2023. The mean dose of collected CD34+ cells has also shown a significant upward trend. The average dose increased from 3.3 x 10^6/kg in the 2007-2012 cohort to 6.2 x 10^6/kg in the 2019-2023 cohort. No improvement was seen in the median PFS during the first two cohort，the PFS of the patient within the last five years was significantly better( median PFS 47.2m vs 76.1m vs NR). The median OS from diagnosis has improved over time with the cohort 1, 2, and 3 having a median OS of 73.3months and 106.1months and NR respectively(P＜0.001). Among patients with high-risk cytogenetics, median PFS and OS increased from 23.2 months and 35.6 months to 60.1 months and NR. After 2018, our center started tandem ASCT for high-risk patients. There was no difference in median PFS between tandem ASCT and single ASCT patients with SRCA ( p = 0.983) .An improvement in median PFS was observed in tandem ASCT patients compared to single ASCT with HRCA patients(p = 0.047). Rates of second primary malignancies were similar in patients transplanted in different time periods. Thrombocytopenia, EME, HRCA, M-protein decline patterns, and MRD positive independently predicted an inferior PFS. Thrombocytopenia, EME, secondary amyloidosis, HRCA, initial treatment regimen with only two drugs and MRD positive independently indicated a poorer OS.

Conclusions: In brief, we illustrated a dynamic landscape of NDMM patients who underwent ASCT in our center. This real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM undergoing upfront ASCT over the past 17 years, and evidently benefited from newly drugs and precise risk stratification.

Disclosures

No relevant conflicts of interest to declare.

This content is only available as a PDF.
2024
Sign in via your Institution