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

Background:

Multiple Myeloma (MM) is a significant hematological malignancy with diverse therapeutic approaches, especially for newly diagnosed multiple myeloma (NDMM) who are transplant-ineligible (TIE). Real-world evidence (RWE) is crucial for understanding treatment patterns and disease progression, which is particularly important for improving outcomes in older patients often underrepresented in clinical trials. The groundbreaking CIMMA study on RWE aims to enhance our understanding of the MM patient journey, disease epidemiology, and treatment practices in Spain.

Aims and methods:

We aimed to assess demographic, clinical, and treatment characteristics of TIE NDMM patients in a multicenter, retrospective and observational study including 8 Spanish hospitals during 2015-2021. We used secondary data from free-text and structured clinical information within Electronic Health Records (EHRs) of TIE NDMM patients, classifying them by age ranges: ≤70, 71-75, 76-80, and >80 years old (y). Clinical information including demographics, disease characteristics, treatment patterns and variables related to efficacy as overall survival (OS) were extracted from patients' EHRs by employing advanced natural language processing (NLP) and machine learning (ML) techniques using EHReadâ (Medsavana, Madrid, Spain) and SNOMED CT. Summary statistics included frequencies for Boolean and categorical variables, and mean, standard deviation, median, or quartiles, for numeric variables.

Results:

Among the 5,396,628 patients screened, 1,899 had MM during the study period, 715 of them (37.6%) being classified as NDMM. Among them, 354 (49.5%) were identified as TIE patients. They presented a median age of 75 (69, 81) y, and when stratified by age group 31.1% were classified as ≤70y, 24.2% between 71-75y, 18.6% between 76-80y, and 26.0% as >80y. The ECOG status analysis showed ECOG 0-1 as the most prevalent, representing 57.7% of reported cases. The International Staging System (ISS) was present in 68.4% of the patients, with 16% belonging to stage III. Creatinine levels were detected in 89.3% of patients with a median (Q1, Q3) of 1(0.8, 1.7) mg/dl. Regarding comorbidities, cardiovascular conditions were registered in 77% of included patients (hypertension 64.7%, atrial fibrillation 23.7%).

Treatment patterns varied depending on patient's age groups. The most common treatments for the 76-80y and >80y groups were Bortezomib + Dexamethasone (Vd) (15.2% [10/66] and 33.7% [31/92], respectively), Bortezomib + Melphalan + Prednisone (VMP) (21.2% [14/66] and 25.0% [23/92] respectively), and Lenalidomide + Dexamethasone (Rd) (33.3% [22/66] and 20.7% [19/92] respectively). In contrast, Daratumumab + Bortezomib + Melphalan + Prednisone (DVMP, 22.0% [19/86]) was the most common treatment for patients between 71-75y followed by Vd (18.6% [16/86]) and Rd (16.2% [14/86]). For younger patients (≤70y), treatment distribution was more homogeneous: Bortezomib + Thalidomide + Dexamethasone (VTD) (15.4% [17/110]), Bortezomib + Lenalidomide + Dexamethasone (VRD) (14.5% [16/110]), Vd (10.9% [12/110]), and Rd (10.9% [12/110]). In the whole population, DVMP showed the highest OS rate at 36 months (96.4%) followed by VRd (88.0%) and Rd (72.8%). OS at 36 months worsened with age: 84.3% in ≤70y group, 86.5% in 71-75y, 75.5% in 76-80y, and 55.1% in >80y.

Conclusions:

The CIMMA study provides critical insights into the demographics, clinical profiles, and treatment patterns of TIE NDMM patients in Spain from 2015 to 2019. It reveals significant age-related differences in treatment and outcomes, particularly with the introduction of monoclonal antibodies in front-line therapies. The addition of daratumumab (DVMP) to conventional regimens has significantly improved 36-month survival rates. However, patients over 80y benefits less from innovative treatments, underscoring an unmet medical need.

These findings highlight the transformative potential of real-world evidence (RWE) in understanding patient journeys and optimizing treatments, especially for the elderly. This study advocates for new RWE initiatives to leverage data for enhancing patient care and fostering a more inclusive, effective, personalized, and responsive to changing needs healthcare system for MM patients.

Mateos:Pfizer: Consultancy, Honoraria; Sanofi: Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy; AbbVie: Consultancy, Honoraria; Kite: Consultancy. Marin Huarte:Johnson & Johnson: Current Employment. Garcia Garcia-Porrero:Johnson & Johnson: Current Employment. Villanueva Forero:Johnson & Johnson: Current Employment. Rios Tamayo:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Hernandez Rivas:Janssen, Roche, Abbvie, AstraZeneca, Beigene, Lilly, Gilead, BMS-Celgene, Amgen, Takeda, Jazz Pharmaceuticals, Rovi, Incyte, MSD: Membership on an entity's Board of Directors or advisory committees; Janssen, Roche, Abbvie, AstraZeneca, Gilead, BMS-Celgene, Amgen, Takeda, Astra Zeneca, Lilly, Beigene: Other: Scientific Talks; BMS-Celgene: Research Funding. Martínez-Lopez:Pfizer: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Incity: Research Funding.