Real-World Evidence of First-Line Therapy in Transplant Eligible Multiple Myeloma Patients: Insights from the Cimma Study

Background: Front line treatment in newly diagnosed multiple myeloma (NDMM) transplantation-eligible (TE) patients remain challenging due to its impact on patients' outcomes. Real-world evidence (RWE) studies are critical for evaluating this population, treatment patterns, effectivity outcomes and safety. The CIMMA study, a pioneering RWE initiative in Spain, aims to transform our understanding of patient journeys, disease epidemiology, and treatment patterns in MM, thereby enhancing patient outcomes and informing future clinical practice and research. Aims and methods : This study aims to assess the demographic, clinical, and treatment characteristics of TE patients diagnosed from MM between 2015-2021 in 8 Spanish hospitals, using natural language processing (NLP) and machine learning (ML). This multicenter, retrospective observational study utilized secondary data from free-text and structured clinical information within Electronic Health Records (EHRs) of patients attended at the participating centers. We used EHRead® (Medsavana) to extract demographics, disease characteristics, treatment patterns, efficacy variables and potential adverse events (AEs). Summary statistics included frequencies for Boolean and categorical variables, and mean, standard deviation, quartiles, or median for numeric variables. Results : Among the 5,396,628 patients attended in the participating hospitals, 715 were NDMM and 226 of them (32%) were identified as TE patients. The median (Q1, Q3) age was 60 (53, 65) years, being the most common treatment regimens VRd in 27.9% of patients (63/226) and VTd in 38.1% (86/226). A total of 72.1% of the population was < 65 years (VRd: 68.2% and VTd: 68.6%). The analysis of ECOG status indicated that ECOG 0-1 was the most prevalent, accounting for 75.4% of reported cases (VRd: 80.0%; VTd: 73.8%). Regarding the International Staging System (ISS), 78.3% of patients were classified as stage I (VRd: 56.1%; VTd: 86.8%). Creatinine levels was reported in 94.2 % of patients with a median (Q1, Q3) of 0.9(0.7, 1.1) mg/dl [VRd: 0.9(0.7, 1) mg/dl; VTd: 0.9(0.7, 1.1) mg/dl]. Cardiovascular were the most common comorbidities and represented 56.2% of patients (VRd: 61.9%; VTd: 52.3%) being present hypertension in 38.9% (VRd: 52.4%; VTd: 36.0%) and atrial fibrillation in 10.2% (VRd: 14.3%; VTd: 5.8%). Overall response rate (ORR) for VRd and VTd was 42.9% and 44.2%, with subsequent complete or better response observed in 19% of VRd and 22% of VTd treated patients. Minimal residual disease (MRD) was analyzed in 37.6% of the included population, being available in 38.1% and 45.3% of patients in the VRd and VTd groups, respectively. The rates of MRD negativity, measured at any point post-treatment initiation, were 11.1% for VRd and 12.8% for VTd. Potential AEs leading to treatment discontinuation occurred in 17.3% of patients with hematological toxicity events reported in 66.4% of patients. They were detected in 19.0% of VRd and in 14.0% of VTd treated patients. Hematological toxicity events related to treatment initiation were reported in 81% and 71% of VRd and VTd groups, respectively. Conclusions : The rapid evolution of MM treatment regimens underlines the critical importance of continuing RWE studies in clinical practice settings in Spain. NLP and ML methodologies that extract data from EHRs have provided crucial insights into treatment patterns and outcomes in this ever-changing environment. The most common therapeutic regimens in NDMM TE were VRd and VTd. Cardiovascular comorbidities were the most common in this group, even among the youngest patients. No differences in efficacy were observed between regimens and safety profiles were generally comparable. Ongoing RWE studies are vital for tailoring MM treatments to ensure they are effective and personalized. Innovations such as the introduction of quadruplet and maintenance regimens (PERSEUS: DVRd+DR) underline the importance of such research for future therapies, crucial to improving the survival and quality of life of patients with MM. Such studies are essential to continually improve patient care and outcomes, ensuring that treatment strategies remain effective, personalized, and responsive to the changing landscape of MM care.