Introduction Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplasms characterized by ineffective hematopoiesis, bone marrow failure, and progression to acute myeloid leukemia. According to the IPSS-R scoring system, they are divided into two major groups for treatment purposes: low-risk (≤3.5 points, LR-MDS) and high-risk (>3.5 points, HR-MDS). Currently, the only approved therapy for high-risk cases is hypomethylating agents, with a median overall survival of 16 months. Given the observed synergy and results with azacitidine and venetoclax (AZA + VEN) in acute myeloid leukemia and the unresolved need in this orphan disease, our objective was to describe the real-world experience in a Latin American cohort using AZA + VEN in HR-MDS patients, who currently have no effective treatment options. Methods Patients with HR-MDS from Argentina, Brazil, Colombia, Ecuador, Mexico, and Uruguay were retrospectively recruited from 2019 to 2023 and included in the Re-GLAM (Latin American MDS Registry). Inclusion criteria were: having HR-MDS with less than 20% blasts and having received at least one cycle of azacitidine with venetoclax. The treatment groups were: 1) HMA + VEN as first-line treatment with the goal of leading to a hematopoietic stem cell transplant (HSCT), and 2) HMA + VEN as second-line treatment. Response was defined using the 2006 IWG criteria, with response (R) being the sum of complete response(CR), partial response(PR), and stable disease(SD), and the rest being considered non-response (NR). Overall survival (OS) was defined from diagnosis to death or last follow-up, and leukemia-free survival (LFS) from the start of treatment to progression to leukemia. Results We recruited 49 MDS patients, 45 (91,8%) with primary MDS, and 34 (69.4%) were men. 98,0% (n=48) had an ECOG ≤2. According to the 2022 WHO classification, the majority had excess blasts type 1 (n=29, 59.2%), with all patients having an IPSS-R score >3.5. The median blasts in bone marrow aspirate was 11% (range;0-19). All received treatment with a hypomethylating agent (48 with azacitidine and 1 with decitabine) plus venetoclax. As first-line treatment in 34 patients (69.4%) and as second-line treatment in the remaining patients. Venetoclax ramp-up dosing was not used, and there were no episodes of tumor lysis syndrome. 95.7% (n=44) received a dose of 400mg, of which 20 adjusted the dose due to antifungal use. 65.3% (n=32) used venetoclax for 14 days. Sixteen patients (32.7%) reached HSCT with a median number of treatment cycles before HSCT of [median 2 (1-12)]. The median follow-up was 41 months (rango; 3-124months). At the last follow-up, 26patients (53,1%) had died. The median OS was 21,9 months (95% CI; 11,6-32,2). When OS was separated by treatment line, no significant difference was found (OS for first-line: 26.96 months (95% CI; 5,4-28,0) vs OS for second-line: 23.8 months (95% CI; 10,7-33,2), p=0.932. The overall response rate (ORR) in the first-line treatment was 67,6% [23/34] (CR 65,2% (15/23), PR 21,7% (5/23), and SD 13,0% (3/23). The median OS for those achieving CR was not achieved (NA) months (95% CI; NA-NA) vs NR:10.71months (95% CI;9.75-11.67), p<0.001. Patients who reached HSCT showed improved OS compared to those who did not (OS: NA months (95% CI; NA-NA) vs 13.11months (95% CI;13.04-30.4), p=0.040. The median LFS was NA months (95% CI NA-NA). The ORR in the second-line treatment was 60,0% [9/15] (CR 55,6% (5/9), PR 33,3% (3/9), and SD 11,1% (1/9)). The median OS for those achieving CR was NA months (95% CI; NA-NA) vs NR: 14.26 months (95% CI 7.84-20.68), p=0.115. The median LFS was 11.76 months (95% CI;7.97-15.56). Conclusion Our real-world evidence (RWE) study includes one of the longest follow-ups of AZA + VEN use in HR-MDS patients. These results suggest that the group that benefits most from the AZA + VEN combination is those who reach HSCT, as it improves OS. The group that does not reach HSCT has a better OS to that observed with azacitidine alone, but onlu in those patients who achieve a CR. No predictive factors of response to AZA + VEN were found, although myeloid mutations were not evaluated, which could potentially explain response probability as seen in other studies.

Background: It is very well known that information provided by clinical records and organized system platforms (registries) offer a holistic view of MDS patients' characteristics and therapeutic aspects in real-life. The primary objective of this study was to analyze data from a novel MDS Latin-American Registry. Methods: The registry started in April 2022. From April to July, patients with MDS or CMML diagnosed since January 2014 were reported from Argentina, Brazil, Colombia, Mexico, and Uruguay. The Research Electronic Data Capture (REDCap) platform was used, consisting of 298 fields to describe patient demographics; their biological characteristics; clinical manifestations; comorbidities; laboratory features; bone marrow studies; risk classification; treatments, and outcomes. According to the Ethics Committee, all subjects had to sign an inform consent. Descriptive statistics were used to summarize demographic, and clinical data, as well as treatment characteristics - overall and by risk groups. Results: A total of 231 patients were included in this analysis. The mean age was 62.8 ± 16.9 years and the male to female ratio was 1.1:1. Baseline characteristics are described in Table 1. According to WHO's 2016 classification, the following categories were reported: MDS-SLD 4.4%; MDS-RS 1.3%; MDS-MLD 34.5%; MDS-RS-MLD 4.4%; MDS-EB 24.9%; MDS with isolated del(5q) 2.2%; unclassifiable MDS 0.4%; therapy-related MDS 7.0%; CMML 10.9%; MDS-U 1.3%; MDS/MPN-RS-T 0.4%; aCML 0.4%; other 7.9%. The IPSS-R was: 3.4% Very Low; 62.3% Low; 17.9% Intermediate; 10.1% high-risk; and 6.3% very high-risk. The majority of patients had de novo MDS (95.2%), and 8.6% had hypoplastic MDS. The mean BM blast count was 3.5±4.3%. Iron staining was performed in 28.1%. BM biopsies were performed at the moment of diagnosis in 77.5% of cases, reported as hypercellular in 90.0% of them and with fibrosis (> grade 1) in 32%. Immunohistochemistry was performed in 53.7% and flow cytometry in 47.8% of patients. Cytogenetics was performed in 93.9% and FISH in 26.9%. Abnormal karyotype was detected in 38.2%. An NGS panel was performed in 35 (15.2%) patients. Low-risk MDS accounts for the majority of patients in our registry (58%). Erythropoietin was given in 73 (69.5%) and growth factor therapy in 13 (11%) patients. Red blood cell transfusion was given to 59 (50%) patients. 31 (26%) of them received second-line treatment: 29 with HMA, and 2 with lenalidomide. 5 (4.2%) underwent allogenic transplant. 16 (13.7%) progressed to AML. The median overall survival was 4.19 (2.7-6.40) years. High-risk MDS was reported in 42% of patients. Regarding treatment, 69 (80.2%) received HMA (AZA=65 and DEC=4), 4 (4.6%) chemotherapy, and 8 (9.3%) of them were administered a venetoclax-based therapy. Fifteen (17.4%) were transplanted and 46 (53.4%) progressed to AML. The median overall survival was 1.5 (1.2-2.0) years. Conclusions: This novel and international registry showed preliminary MDS data from Latin-America. Our results revealed younger age at diagnosis, high number of patients undergoing allogenic transplant and OS according to literature. The expansion of this registry certainly improves our clinical practice. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Introduction Rituximab is a chimeric monoclonal antibody designed against the CD20 receptor displayed on the surface of B cells and used to treat nearly all B-cell non-Hodgkin lymphomas (NHLs). It was the first monoclonal antibody approved in oncology and it has improved outcomes in all B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. In recent years, the approval of several rituximab biosimilar molecules worldwide has further improved the patients' access to this drug, promoting cost-effective treatment. Biosimilar molecules are defined by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) as a biological molecule product highly similar to the approved reference product with no clinically meaningful differences. The multicentric double-blind international prospective pivotal study RTXM83-AC-01-11 led to the approval of rituximab biosimilar RTXM83. The study evaluated the efficacy, pharmacokinetics (PK)/pharmacodynamics (PD), safety, and immunogenicity profile of RTXM83 (rituximab biosimilar) vs reference rituximab (Mabthera®), both with CHOP, as first-line treatment of Diffuse-Large-B-Cell-Lymphoma (DLBCL). Participants from both arms received 6 cycles of R-CHOP followed by a 9-month follow-up (Candelaria et al., 2019). Data regarding long-term efficacy and safety events are of great relevance to demonstrate the strength of the clinical response and deepen the confidence in the use of biosimilar molecules. Here, we present a partial data analysis regarding the long-term safety of 11 patients included in this retrospective observational study. Aim This national retrospective observational study aimed to collect long-term data regarding safety e efficacy outcomes from Brazilian participants of the pivotal study RTXM83-AC-01-11 which led to the approval of biosimilar rituximab (Vivaxxia®) in Brazil. Methods All 28 Brazilian participants that were randomized and completed the phase III study RTXM83-AC-01-11 were eligible for this observational, retrospective LB2002 study (Clinical trial information: NCT04928573). Participants were invited to sign the consent form and share the disease history collected since their randomization on the RTXM83-AC-01-11 study. This partial analysis shows the participants' demographic and baseline characteristics, baseline disease characteristics, and the long-term safety data collected and monitored until July 1st, 2022. The long-term safety endpoint was the frequency of serious adverse events of interest, and we considered in this analysis the time between the end of the RTXM83-AC-01-11 study and the consent date of the LB2002 study. Results The intention to treat (ITT) and Safety populations comprised the partial analysis of the same 11 participants, 7 of them (63.6%) treated with biosimilar RTXM83 plus CHOP and 4 (36.4%) with Mabthera® plus CHOP. The median study follow-up time was 73.3 months, considered in this analysis as the time between the randomization of RTXM83-AC-01-11 study participants and the consent date of the LB2002 study. Overall, participants' median age was 55 years old, 63.6% were white, 54.5% were female, 18.8% were active smokers and the body mass index (BMI) ranged from 20 to 35.7 Kg/m² (Table 1). Regarding disease characteristics, 9,1% of the overall participants were classified as stage I DLBCL, 45.5% stage II and IV at the time of diagnosis. Of all 11 participants, 72.7% displayed extranodal lesions, and 18.2% had bulky lesions with a median body surface area (BSA) of 1.8 m2 (Table 1). As for prognostic factor and performance status, participants were classified with IPI 1 (45.5%) and 2 (54.5%), ECOG 1 (72.7%) and 2 (18.3%). The long-term safety analysis from the 11 participants revealed that 2 participants (18.2%) suffered from serious adverse events (SAE) among those of interest listed in Table 2. One participant of the RTXM83-CHOP arm had a SAE classified as severe infection related to rituximab (hypogammaglobulinemia). From the R-CHOP/MabThera® 1 participant displayed 1 SAE (secondary neoplasm) with a possible relationship to rituximab. Conclusion The partial analysis of the LB2002 has demonstrated thus far the safety profile of the biosimilar RTXM83 (Vivaxxia®) in the Brazilian population is consistent with the known safety profile of rituximab. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

PURPOSE:Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL.METHODS:This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4).RESULTS:Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.CONCLUSION:The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

Methods: RTXM83 is a proposed biosimilar developed by mAbxience S.A. to the reference medicine product rituximab (MabThera®/ Rituxan®). A prospective, multicenter, double-blind, randomized trial compared the efficacy in terms of non-inferiority, pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity of RTXM83 vs rituximab (Mabthera®/Rituxan®), both in combination with CHOP chemotherapy (RTXM83-CHOP vs R-CHOP), as first-line treatment in patients with previously untreated CD20+ Diffuse Large B Cell Lymphoma (DLBCL). Adults aged ≥18 and ≤65 years, with a disease stage of I (only with bulky disease) to IV according to the Cotswolds modification of the Ann Arbor classification, and ECOG performance status ≤2 were included, and randomized (1:1) to receive up to a total of six cycles of either RTXM83-CHOP or R-CHOP. Patients were stratified according to study center and age-adjusted IPI scores (0 versus 1), which are based on: disease stage, ECOG, and lactate dehydrogenase (LDH) levels.

Introduction: There are few reports of standard of care and outcomes in Latin America. The HOLA study is a retrospective chart review of patients with B-cell malignancies in Latin America (LATAM).