A Brazilian Real-Life Experience of Multiple Myeloma Patients: Final Results from the Mmybrave Multi-Center Study

Background: Despite incremental therapeutic improvements for patients (pt) with multiple myeloma (MM) over the past two decades, large discrepancies still exist worldwide in outcomes and in terms of access to novel agents and stem-cell transplantation (SCT). Moreover, the real-world effectiveness of novel therapies may not reflect pt profiles and outcomes from clinical trials. Management of MM in Brazil is subject to constraints that may impact clinical outcomes, and continual assessment of trends in treatment patterns and results in real life is warranted.

Methods: The objective of MMyBRAve (NCT03506386) was to investigate the demographic and clinical characteristics, as well as the patterns of care and treatment results, for patients with MM treated at selected experienced hematology/oncology centers in Brazil. Eligible pts were aged ≥18 years and had been diagnosed with MM using contemporaneous IMWG criteria between 01/2008 and 12/2016. Demographic and clinical data were collected from institutional charts retrospectively between 06/2018 and 08/2019 using a dedicated electronic case report form. Treatment and patient evaluation were left to local standards of care. Baseline pt and disease characteristics, as well as treatment patterns, were analyzed descriptively. The overall survival (OS) was analyzed using the Kaplan-Meier method, and predictors of OS were explored using Cox proportional-hazards model. The OS was compared between subgroups defined according to selected baseline characteristics, eligibility to transplantation (Tx) at baseline, and type of institution (public vs private).

Results: 17 institutions (Inst) contributed data from 943 pts, who had a mean age of 68.4 years (range, 29 to 103). Females comprised 46.3% of the pts, and 61.1% were reportedly White. Considering the 792 pts with information on immunoglobulin (Ig) isotype, 57.7% had IgG, 21.2% IgA, 16.9% light-chain only, non-secretory in 3.5%, and IgD, IgE or IgM in 0.6%. International Staging System (ISS) stage at diagnosis was I in 19.3%, II in 21.3%, III in 26.6%, and unknown in 32.8%. 491 (52.1%, 95% confidence interval [CI], 48.9% to 55.3%) pts were considered Tx-ineligible at baseline. 452 (47.9%, 95% CI, 44.7% to 51.1%) pts were considered Tx-eligible, and 250 (55.3% of 452; 95% CI, 50.6% to 60.0%) underwent Tx as part of frontline therapy. Overall, after a median follow-up of 63 months, the median OS was 70 months, with OS probabilities of 87% at 12 months, 78% at 24, 70% at 36, 62% at 48, and 55% at 60 months. Tx-ineligible pts were significantly older and had significantly higher levels of creatinine and lactic dehydrogenase (LDH), and more advanced ISS than Tx-eligible pts. Median OS times were 49 and 93 months for Tx-ineligible and Tx-eligible patients, with a hazard ratio (HR) of 0.52 favoring Tx-eligible (95% CI, 0.43 to 0.63; P<0.001). 519 pts came from public Inst, and 424 from private. The former had significantly lower levels of hemoglobin and significantly higher levels of creatinine, calcium and LDH, and more advanced ISS than pts from private Inst. Median OS in these two groups were 61 and 74 months, with a HR of 0.78 favoring pts from private Inst (95% CI, 0.64 to 0.94; P=0.010). Pts from public Inst were more likely to receive melphalan- or thalidomide-based frontline regimens, whereas those from private Inst were more likely to receive bortezomib in frontline. Other univariable baseline factors associated with OS were age, hemoglobin, creatinine, calcium, and Durie-Salmon stage. In multivariable analysis for factors associated with OS, all these remained significant, and so was Inst (HR=0.61, P=0.002). Although there was no significant difference in Tx eligibility between public and private Inst (46.1% vs 50.2%; P=0.224) or in the percentage of patients undergoing Tx (24.5% vs 29.0%; P=0.134), adding this variable to the multivariable model for OS suggested that it confounds the association between type of Inst and OS, since Tx eligibility became a stronger prognostic factor (HR=0.586, P<0.001) than type of Inst (HR=0.81, P=0.073).

Conclusions: Comparing these results with those from previous studies, the OS of pts with MM is improving in Brazil. Discrepancies remain in OS for patients from public and private institutions. Although the reasons for this finding remain to be ascertained, differential access to novel therapies cannot be ruled out as a determining factor.

Hungria:Amgen: Honoraria; GSK: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Bristol Myers Squibb: Honoraria. Bittencourt:Takeda: Membership on an entity's Board of Directors or advisory committees. De Farias:Takeda: Speakers Bureau. Carvalho:Takeda: Current Employment. Senra:Takeda: Current Employment. Abreu:Takeda: Current Employment.