Evaluation of Clinical Characteristics and Prognostic Factors of Early Progressive Disease (EPD) in Newly Diagnosed Multiple Myeloma Patients: Real-World Data of the Greek Myeloma Study Group.

Abstract

Background: Despite treatment improvements a considerable proportion of newly diagnosed multiple myeloma (MM) patients experience early progressive disease (EPD) defined as progression or relapse in < 18 months following initial response to first line treatment.

Methods: We evaluated 1436 newly diagnosed MM patients out of whom 23.3% had EPD.

Results: Patients with EPD had higher median age, β2-microglobulin, LDH and lower hemoglobin and eGFR, compared to others (P < .05); EPD population presented more commonly with advanced stage (ISS3, RISS3, and R2-ISS stage III/IV). Ultra-high-risk MM (UHR-MM) i.e., detection of ≥ 2 high-risk molecular abnormalities was more frequent in EPD population (P < .001). The percentage of patients treated with lenalidomide-based regimens was not significantly different. Daratumumab-based therapies (DBT) were administered less frequently in patients with EPD (2% vs. 10%; P < .001); 11% of patients with EPD versus 33% underwent ASCT (P < .001); Complete response to induction therapy was significantly lower in EPD patients (12% vs. 27%; P < .001). Binary logistic regression analysis demonstrated that ISS, RISS, R2-ISS, UHR-MM, ASCT and DBT were significant predictors for EPD (P < .05). In multivariate analysis R2-ISS, ASCT, and DBT were independent prognosticators for EPD (P < .001). Median PFS and OS were 10 versus 40 months and 29 versus 76 months in patients with EPD versus others, respectively (P < .001).

Conclusion: In real-world, EPD is observed in more than one-fifth of patients, and it remains an unmet clinical need. Daratumumab-based therapies and ASCT significantly reduce the probability of EPD, while R2-ISS could serve as a useful prognostic tool for recognizing this population and guide therapeutic decisions.