Treatment Practices and Rechallenge in Multiple Myeloma Patients: Real-World Evidence in Argentina (TOTEMM-A) and Brazil (TOTEMM-B)
Authors: Abreu Gabriela A , Queiroz Juliana , Nogueira da Silva Thiago Luiz , Soares Claudia R , Menezes Patricia , Carrizo Mariano , Ricca Tatiana , Pires Tatiana , Tanaka Straus , Perelli Lucas , Bernardino Graziela , de Souza André Luiz Alves Ribeiro , Simonovich Ventura , Scibona Paula , Seehaus Cristian M , Brulc Erika B , Kim Natalia , Jotimliansky Laura 
Published: December 2024

Introduction: Real-world data on treatment duration and clinical outcomes among patients with multiple myeloma (MM) in Latin America are limited. 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 provide real-world evidence of duration of treatment (DOT), time to next treatment (TTNT), treatment-free interval (TFI), time to first relapse, and proportion of patients receiving a rechallenge with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), or anti-CD38 monoclonal antibody (mAb) (daratumumab), alone or in combination, in both countries.

Methods: Both studies comprised a retrospective database analysis. TOTEMM-A used private 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 term and any treatment (stem cell transplant [SCT] and/or antineoplastic drug). Patients had ≥12 months of follow-up after index. MM treatment was evaluated from index date to loss to follow-up, death, or end of study period, whichever occurred first. Line of therapy (LOT) from first (1L) to fourth line (4L) was defined as drug combination(s) and/or SCT received within 30 days from initiation of treatment course, and ended upon cessation of those drugs or at initiation of a drug not part of the current LOT. DOT was defined as the time from the first to the last treatment received within a LOT, in months. TFI was defined as the time from the end of a LOT to the beginning of the subsequent LOT, whereas TTNT was defined as the time from the beginning of a LOT to the beginning of the subsequent LOT, in months. Patients with relapsed MM were identified as those who had received ≥2 LOTs and previous exposure to a PI, IMiD, or anti-CD38 mAb (daratumumab), alone or in combination. Time to first relapse was calculated as the time from the beginning of a LOT with a PI, IMiD, or anti-CD38 mAb (daratumumab), alone or in combination, to the beginning of the subsequent LOT, in months. Rechallenge was defined as retreatment with a PI, IMiD, or anti-CD38 mAb (daratumumab), alone or in combination, after relapse.

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. In TOTEMM-A, two-fifths of the patients with MM received ≥4 LOTs, and in TOTEMM-B, one third. Median DOT in the 1L, second line (2L), third line (3L), and 4L was 5.5, 3.9, 3.8, and 2.9 months in TOTEMM-A and 4.4, 3.3, 3.5, and 3.7 months in TOTEMM-B, respectively. Median TFI from 1L to 2L, 2L to 3L, and 3L to 4L was 1.5, 3.2, and 3.4 months in TOTEMM-A and 1.0, 1.2, and 1.0 months in TOTEMM-B, respectively. Median TTNT from 1L to 2L, 2L to 3L, and 3L to 4L was 8.2, 8.6, and 8.7 months in TOTEMM-A and 6.7, 4.5, and 4.5 months in TOTEMM-B, respectively. Approximately 70% of patients in both countries who had previous exposure to a PI, IMiD, or anti-CD38 mAb (daratumumab), alone or in combination, experienced relapse at any time; most were exposed to only PI (TOTEMM-A, 62.6%; TOTEMM-B, 77.2%); 24.2% and 2.3% were exposed to only IMiD, respectively; in TOTEMM-B, 2.1% were exposed to only anti-CD38 mAb (daratumumab). Median time from beginning of exposure to first relapse was 10.3 months in TOTEMM-A, and 8.3 months in TOTEMM-B. After relapse, in patients who received ≥2 LOTs, most patients in TOTEMM-A were re-treated with thalidomide (72.7%), and in TOTEMM-B, 61.3% with bortezomib, and 9.5% with an anti-CD38 mAb (daratumumab).

Conclusions: These real-world data on clinical practices in Argentina and Brazil show that although many patients with MM in both countries experience relapse after previous exposure to a PI, IMiD, or anti-CD38 (daratumumab), alone or in combination, most continue to receive the same treatment. This highlights the high unmet medical need in this population and the need for new and effective treatment options.