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    MRD and Biomarkers

    Category: MRD and Biomarkers

    Characteristics of Long-Term Survivors in Multiple Myeloma: Exploring Factors for Cure After Extended Folow-Up

    (PA-163) Characteristics of Long-Term Survivors in Multiple Myeloma: Exploring Factors for Cure After Extended Folow-Up

    Thursday, September 18, 2025

    Introduction:      Multiple myeloma (MM) is typically characterized by successive relapses, with cure rarely considered. Clinical trials often have limited follow-up due to costs, and real-world studies face challenges like small sample sizes or heterogeneous management. Thus, data on long-term MM survivors are scarce, and late relapses challenge the concept of operational cure. This study analyzes factors associated with long-term survival in a large, homogeneously treated cohort with extended follow-up.

    Methods:   We analyzed 1,018 transplant-eligible, newly diagnosed MM patients treated from 1999-2004 with polychemotherapy (VBMCP/VBAD), transplant, and 2-year maintenance (interferon/prednisone) under the GEM2000 protocol. Clinical and biological data were collected and updated to the last follow-up.

    Results:   With a median follow-up of 180 months (95%CI 156-256), median overall survival (OS) was 69 months (95%CI 62-74), with 10-, 15-, and 20-year OS probabilities of 30%, 20%, and 12%. The probability of being alive and disease-free at 10 and 15 years was 14% and 6%. In multivariate Cox regression, factors associated with better OS included age < 65 years, ECOG < 2, standard-risk cytogenetics, hemoglobin >10 g/dL, and platelet count >150,000/µL. These factors, plus female sex, predicted long-term survival (≥15 years) in multivariate logistic regression. Achieving undetectable minimal residual disease (MRD, ≥10⁻⁴ sensitivity) post-transplant was the strongest predictor when included in both analyses, with median progression-free survival of 74.4 months (HR 0.47; 95%CI 0.35-0.64) and OS of 193.2 months (HR 0.48; 95%CI 0.35-0.65). Relative survival was lower than the age-, sex-, and date-adjusted Spanish population, with excess mortality persisting at 10 and 15 years. Of 806 deceased patients, 40.7% died from progression, 21.8% from MM-related causes (mainly infections), 11.3% from unrelated causes, and 26.2% had unknown causes. Non-MM-related mortality was 9.4% in those dying within 5 years vs. 35.6% beyond 15 years (OR 7.67; 95%CI 3.35-18.20).

    Conclusions:   This series, with one of the longest follow-ups reported, identifies a long-term survivor population, mainly driven by MRD negativity, whose characterization may optimize treatment intensity and costs. Nevertheless, excess mortality persists even in long-term survivors, suggesting true cure remains rare in the pre-novel therapy era.