Comparison of Clinical and Laboratory Features, Drug Availability, and Outcomes of CLL Patients Treated in Public or in Private Hospitals in Brazil: A Retrospective Analysis of the Brazilian Registry of CLL

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) typically occurs in elderly patients and has a highly variable clinical course. It is important to understand the aspects that affect the outcomes of CLL in a real-world setting. Besides biological factors, other socioeconomic and health system factors may influence the clinical course of CLL. Hence, data from the Brazilian Registry of CLL was analyzed to compare clinical and treatment-related characteristics in patients with CLL treated in public or in private institutions in Brazil. Objective: To describe the outcomes of a series of CLL patients followed in public or in private hospitals in Brazil. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective non-interventional data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. For this analysis, we included all patients with minimum available data for analysis of patient and disease characteristics and survival. Results/discussion: From January 2004 to July 2020, 2927 patients from 37 centers met eligibility criteria for this analysis: 2324 (79%) were followed at public hospitals and 603 (21%) at private hospitals. The majority were male (57%), with median age of 65 years (ranging from 23 to 106). Binet stage was A in 1618 (58%) patients, B in 628 (23%) and C in 525 (19%). FISH for del(17p) was performed in only 479 patients (16%), while FISH for the most common aberrations [del(13q), +12, del(11q), and del(17p)] was performed in only 445 patients (15%). IGVH mutational status was performed in only 211 patients (7%), and karyotype in only 140 patients (5%). Comparing public and private hospitals, we observed that patients in public hospital are slightly older (median age 66 years vs. 64 years for private hospitals, P=0.04), had more advanced diseases at diagnosis (frequency of Binet B or C was 44% in public vs. 32% in private hospital, P<0.0001), and there were more patients with elevated creatinine levels (14% vs. 10%, P=0.03). All prognostic markers were significantly more available in private than in public hospitals: FISH for del17p (42% of cases vs. 10%, respectively, P<0.0001), IGVH mutational status (13% vs. 6%, respectively, P<0.0001) and karyotype (16% vs. 2%, respectively, P<0.0001). The frequency of del(17p) was similar between public and private hospitals (10% vs. 11%, P=NS), while the frequency of unmutated IGHV status was more common in private hospitals, although not statistically different (60% vs. 48%, P=0.09). Analyzing 2102 diagnosed after 2010, we observed that 864 patients (41%) were treated after a median time of 7 months (range: 0-267) after diagnosis. First line treatment was predominantly based chlorambucil (45%) or fludarabine (40%). Anti-CD20 monoclonal antibody was used in only 39% of cases: (rituximab in 35% and obinutuzumab in 4%). Novel agents were used in first line in only 2% of patients, and in most cases in the context of a clinical trial. Of note, most patients (86%) with del(17p) detected by FISH were treated with chemoimmunotherapy. When comparing treatments between public or private hospitals we observed striking differences: in public hospitals there were significantly less patients receiving fludarabine-base regimens (36% vs. 54%, P<0.0001), and anti-CD20 monoclonal antibodies (28% vs. 78%, P<0.0001). Overall survival at 6 years was significantly worse in public than in private hospitals (72% vs. 93%, respectively, P<0.0001). After a multivariate analysis, survival in patients from public hospitals remained significantly worse than in private hospitals (hazard ratio 3.4, 95% confidence interval 2.4 - 4.8), after correcting for age, Binet staging and renal function. Conclusion: Our data indicate that are striking differences between patients treated in public or private hospitals in Brazil. The lack of accessibility to basic laboratory tests for prognostic factors and adequate therapies probably explains the worse outcome of patients treated in public institutions. In fact, prognostic testing rates were poor in both contexts and most high-risk patients received chemoimmunotherapy first-line. Urgent strategies are needed to increase accessibility to prognostic testing and to novel agents for quality improvement in health care in CLL patients in Brazil. Disclosures No relevant conflicts of interest to declare.

Management of Chronic Lymphocytic Leukemia in Less-Resourced Countries

“…Summary results from the latest publications showing the overall profile of patients are shown in Table 2. 25,26 In addition to the registry, the Brazilian Group of CLL was created in 2013, with the aim of providing treatment recommendations and foster patient enrolment in clinical trials. 28 With a population of 3.4 million inhabitants, Uruguay is one of the smallest countries in South America and has an ethnic distribution that comprises 87.7% of Whites, 4.6% of Blacks, 2.4% indigenous, and 5.3% other or unspecified.…”

“…25 Moreover, these data indicate that there are striking differences between patients treated in public and private hospitals in Brazil, something that may underlie the disparities in outcomes seen in Brazil and in other countries and settings in oncology. 26,[31][32][33][34][35] Data from the Brazilian Registry of CLL were used to compare patient profile and management in patients treated at public or private centers. 26 Of 3031 patients meeting eligibility criteria, 80% were followed at public hospitals and 20% at private hospitals between January 2004 and July 2020.…”

“…26,[31][32][33][34][35] Data from the Brazilian Registry of CLL were used to compare patient profile and management in patients treated at public or private centers. 26 Of 3031 patients meeting eligibility criteria, 80% were followed at public hospitals and 20% at private hospitals between January 2004 and July 2020. Patients from public hospitals were slightly older (median age, 66 vs. 63 years; P < 0.001), had more advanced diseases at diagnosis (Binet B or C stages in 44% vs. 33%; P < 0.001), and more often had increased creatinine levels (18% vs. 10%; P = 0.03) than patients from private hospitals.…”

“…Once again using Brazil as an example, given the availability of published data, a contrast can be made between patients with CLL seen at public and private institutions. 26 Testing for prognostic markers for CLL is more often available in private than in public hospitals in Brazil: testing of 17p deletion by fluorescent in situ hybridization (42% vs. 10%), mutational status of the immunoglobulin heavy-chain variable region (13% vs. 6%), and karyotype (16% vs. 3%) are all significantly (P < 0.001) more commonly available in private centers, notwithstanding their scarcity even in such centers. When assessed, the frequency of 17p deletion was similar between public and private hospitals (10% vs. 11%), whereas an unmutated immunoglobulin heavy-chain variable region status was nominally more common in private hospitals (60% vs. 48%).…”

“…As of September 2020, 4519 patients had been enrolled from 37 centers (28 public and 9 private). Summary results from the latest publications showing the overall profile of patients are shown in Table 2 25,26 . In addition to the registry, the Brazilian Group of CLL was created in 2013, with the aim of providing treatment recommendations and foster patient enrolment in clinical trials 28 …”