Importance of Access Inequality and Biological Prognostic Factors in Mantle Cell Lymphoma Outcomes in Brazil: A Real-World Evidence Study from a Third World Country

Introduction:Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma with a heterogeneous clinical course. Prognostic factors such as MIPI status, Ki-67, and P53 are crucial for therapeutic decisions. Intensive rituximab-cytarabine-based induction followed by autologous stem cell transplantation (ASCT) is often the best therapy. Most real-world evidence (RWE) comes from developed countries with broad access to modern therapies. RWE studies highlight the impact of prognostic factors in diverse populations and differences in diagnostic and therapeutic support across socioeconomic contexts.

Objective:This study aimed to describe the epidemiologic characteristics, types of therapy, and clinical outcomes of Brazilian MCL patients diagnosed between January 2010 and December 2023 and compare outcomes by treatment site (public vs. private) and Ki-67. Patients treated in the public system has generally no access to rituximab for MCL.

Methods:Records were collected from 9 institutions across Brazil. Only cases with CyclinD1 and/or SOX11 positivity were included. Data was entered into an eCRF. Statistical analysis was performed using SPSS software. Survival curves were generated using the Kaplan-Meier method and compared with the Log Rank test.

Results: A total of 137 patients (95m, 42f) were analyzed. The median age at diagnosis was 64.5y (24-96y). ECOG performance status was 0 or 1 in 88 patients. Leukocytosis was present in 47 patients. MIPIrisk groups were determined in 92 patients, with 44 classified as high risk. The Ki-67 was obtained in 88 patients, with 23 showing ≥ 50%. 73 patients had histologic classification: 48% classical, 14% blastoid/pleomorphic, and 30% indeterminate. ASCT were performed in 61 patients (44%). 79 patients (58%) were treated in public institutions, and 63 (46%) received intensive therapy (IT). Among younger patients (<70y), 58% (57/98) received intensive therapy, and 46.9% underwent ASCT. Immunohistochemistry for P53 was found in 19 patients. The median overall survival (mOS) was 3.9y (0.01-15.4y) for living patients. Progression-Free Survival was 1.9 y. At last follow-up, 68 patients were alive. The Ki-67 index (≥ 50%) correlated with adverse prognosis (3.4y vs. 5.5y, P=0.017). mOS according to MIPI was 4.9y for low/intermediate vs. 4.5y for high scores (P=0.05). ASCT patients had a mOS of 6.1y compared to 5.0y for non-ASCT patients (P=0.011). IT regimens resulted in a mOS of 7.1y vs. 4.3y for mild regimens (P=0.010). Rituximab in first-line treatment resulted in a mOS of 6.4y vs. 4.4y for non-users (P=0.05). Among patients <70y, IT showed reduced mOS compared to non-IT (7.3y vs. 4.6y; P=0.022) and ASCT (6.1y vs. 5.2y;P=0.04). Patients in the private healthcare system had a mOS of 7.6y compared to 4.2y for those in the public system (P=0.007).

Discussion and Conclusion:This RWE study elucidates the landscape of MCL in Brazil and the healthcare challenges amid socioeconomic inequality. The median age at diagnosis aligns with studies from developed countries, showing good sample representation. However, critical staging data such as KI67, MIPI, and P53 are not routinely available at diagnosis. Many eligible patients (<70y) did not undergo ASCT (53.1%), raising concerns about procedure accessibility. IT significantly improved OS, suggesting it as an alternative to ASCT There is a discrepancy in OS between public and private patients (4.2y vs. 7.6y), highlighting the need to understand contributing factors. The improvement in survival with Rituximab in the first-line treatment underscores the need for its availability in the public system. The PFS and OS were generaly worse than the ones from clinical controled studies. Studies comparing prognostic factors in 3rd world populations are essential.