Introduction: Multiple myeloma remains incurable despite treatment advances that have significantly improved progression-free survival (PFS) and overall survival (OS). In a recent single-center retrospective analysis of 323 patients with newly diagnosed multiple myeloma (NDMM), Dimopoulous et al., identified 49 patients who achieved an OS of more than 15 years, including 25 who were progression-free. Compared to the patients with PFS of less than 15 years, the long-term PFS group had lower median age, higher prevalence of International Staging System (ISS) 1 disease, lower proportion of high-risk cytogenetic abnormalities, and were more likely to receive autologous stem cell transplantation and maintenance therapy. These findings suggest that a distinct subset of patients can achieve durable disease control, highlighting the importance of identifying clinical or biological predictors of prolonged PFS.

Methods: We conducted a retrospective cohort analysis of 1000 consecutive NDMM patients treated with lenalidomide, bortezomib and dexamethasone (RVD) induction therapy followed by risk-adapted maintenance therapy diagnosed from September 2007 to August 2016 at Emory University to identify and characterize patients with long PFS (≥10 years) (Joseph et al JCO 2020). Date of last data review was June 30th, 2025. We excluded patients diagnosed after June 30, 2015, as they had not met the 10-year follow-up threshold. Demographics, clinical characteristics, and outcomes data were obtained from our institutional review board-approved myeloma database and through manual abstraction.

Results: Out of the 1000 NDMM, 164 patients diagnosed after June 30, 2015 were excluded from analysis. Among the remaining 836 eligible patients, we identified 143 patients who achieved a PFS of ≥10 years. These long-term responders were more likely to be ≤65 years old (77.6%) compared to the overall NDMM cohort (66.0%). The racial composition was similar between the two groups, with Black patients comprising 34.4% of long-term responders and 35.2% of the overall cohort. The IgG isotype was the most common in both cohorts, present in 64.5% of long-term responders and 59.2% of the overall cohort. Long-term responders were more likely to have R-ISS I (54.7%) compared to the overall cohort (16.3%). Long-term responders were less likely to have a hemoglobin (Hb) <10 at diagnosis (26.4%) compared to the overall cohort (34.3%). The long-term responders included 20.8% high risk patients, defined at that time as presence of del 17p, t(4;14), t(14;16) or abnormal conventional cytogenetics, compared to 25.1% in the overall cohort. 80% of long-term responders compared to 75.1% of the overall cohort underwent upfront autologous stem cell transplantation. A greater proportion of long-term responders received maintenance therapy (85.9%) compared to the overall cohort (75.3%).

Conclusion: In this large, single-center retrospective cohort study, we identified 143 NDMM who achieved prolonged disease control, maintaining a PFS of ≥10 years. Long-term responders were more likely to be younger, be stage R-ISS I, have higher Hb levels at diagnosis, and receive maintenance therapy. Among these long-term responders, 20.8% had high-risk disease. Further research is needed to better understand this subset of high-risk disease patients with prolonged PFS to determine whether these outcomes reflect evolving definitions of high-risk disease or the impact of risk-adaptive maintenance strategies. Further analysis will include assessment of PFS from the 10-year landmark, comparison to the entire cohort as well as testing the ability of this cohort to predict long term survival in current therapy with four drug treatment regimens.

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2025
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