Multiple Lines of Therapy and Progression to Next Lines in Multiple Myeloma Patients: Real-World Studies in Argentina (TOTEMM-A) and Brazil (TOTEMM-B)

Introduction: Despite treatment advances in the past decade, multiple myeloma (MM) remains incurable. Patients typically need successive lines of therapy (LOTs) based on several drug combinations to treat relapsed disease. Proportions of patients reaching the subsequent LOT decline gradually and most patients are still unable to receive second and later LOTs. To the best of our knowledge, there are no real-world studies evaluating how the progression to subsequent LOTs occurs in patients with MM treated in Latin America. The aim of the TOTEMM study was to report on treatment patterns and clinical progression in patients with MM in Argentina (TOTEMM-A) and Brazil (TOTEMM-B). Here, we evaluated the proportion of patients with MM who did not progress to subsequent LOTs in both countries. Methods: Both studies comprised a retrospective database analysis. TOTEMM-A used electronic medical records from Hospital Italiano between Jan 2010 and Dec 2021, and TOTEMM-B used private administrative claims data from Orizon between Jan 2015 and Jun 2021. Index was defined as a proxy of diagnosis and could be the first MM-related health term or International Classification of Diseases, 10th revision (ICD-10) code, or any related procedure, examination, or treatment for MM. Eligible patients included adults aged ≥18 years with ≥1 MM ICD-10 code (C.90) or MM-related health terms and any treatment (stem cell transplant [SCT] and/or antineoplastic drugs). Patients had ≥12 months of follow-up after index. MM treatment was evaluated from index to loss to follow-up, death, or end of study period, whichever occurred first. LOT was defined as drug combination(s) or SCT, or both, received within 30 days from initiation of treatment course, and ended upon cessation of those treatments, or at initiation of a drug not part of the current LOT. Proportions of patients progressing and not progressing to the subsequent LOT were calculated from first (1L) to fourth line (4L). Results: In TOTEMM-A and -B, 134 (45.5% male; mean age 70.9 [standard deviation (SD) 11.6] years) and 736 (53.8% male; mean age 61.9 [SD 11.3] years) patients with MM from the incident cohort were included, respectively. Mean (SD) number of LOTs for TOTEMM-A was 3.7 (2.5) and ranged from 1 to 15, and for TOTEMM-B, was 3.0 (1.7) and ranged from 1 to 12. Mean (SD) time of follow-up was 58.9 (32.6) months in TOTEMM-A, and 30.6 (14.3) months in TOTEMM-B. In TOTEMM-A, 17.9% of patients did not progress from 1L to second line (2L), 20.9% from 2L to third line (3L), and 33.3% from 3L to 4L; in TOTEMM-B 17.9%, 34.3%, and 43.3% did not progress to subsequent LOTs, respectively. In TOTEMM-A, half of the patients who progressed to subsequent LOTs reached the 4L in 2 years, and in TOTEMM-B, in 1 year. Conclusions: These data highlight that patients with MM in Argentina and Brazil are treated with multiple LOTs and progress to subsequent LOTs in a relatively short period of time. There is a need for treatments that prolong or prevent disease progression in the 1L setting to improve long-term outcomes. With approximately 18-40% of patients not progressing to later LOTs in both countries, these results reinforce the importance of using the best agents first to increase the probability of patients benefitting from novel treatments that could improve outcomes in this high-risk population.