Abstract: 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.

Abstract: The incidence of multiple myeloma (MM) has surged globally, particularly in Latin American countries, and is attributable to an aging population and increased life expectancy. This systematic review analyzes the epidemiology, patient characteristics, and treatment outcomes for MM in selected Latin American countries: Brazil, Mexico, Colombia, Argentina, Chile, Peru, and Uruguay. PubMed and the Latin American and Caribbean Health Sciences Literature (LILACS), conference abstracts (between June 2019 and June 2022), and GLOBOCAN registry (January 2010 to June 2022) were electronically searched. Qualitative analysis employed the Joanna Briggs Institute's critical appraisal tool. Among the 586 screened articles, 26 met the inclusion criteria. The participants’ median age ranged from 54 to 67 years. GLOBOCAN data revealed that for MM, Brazil and Uruguay had the highest and lowest incidence, 5‐year prevalence, and mortality, respectively. Immunoglobulin G was the most common subtype detected. Stage III was frequently diagnosed. Though many approved drugs are available and bispecific antibodies hold promise as a future therapy, limited access, especially for CAR‐T cell‐based therapy remains a concern. The incidence of MM is increasing in Latin America. Resource constraints and costs hinder access to novel drugs and regimens. Understanding disease patterns and patient characteristics is vital to improve MM management in these countries.

Abstract: Abstract 3976 Background: The outcomes of patients with multiple myeloma (MM) have significantly improved in recent years mainly because of the availability of 2 novel classes of drugs: immunomodulatory drugs (IMiDs; thalidomide and lenalidomide) and proteasome inhibitors (bortezomib). However, a subset of MM patients is refractory to these agents, and responding patients often relapse or progress. Therefore, novel salvage treatments are needed. Panobinostat is an oral pan-deacetylase inhibitor (pan-DACi) that has demonstrated synergy in combination with bortezomib in preclinical MM studies. This synergy is thought to occur through inhibition of protein metabolism via targeting of the aggresome and proteasome pathways. Significant clinical activity, including complete responses, was observed in a phase Ib study of panobinostat + bortezomib in patients with relapsed or relapsed and refractory MM (San-Miguel et al, EHA 2011, abstract 0314). In addition, responses were observed in patients with bortezomib-refractory MM. Based on these preliminary data, a phase II and III clinical study program of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed or refractory MM was initiated—PANobinostat ORAl in Multiple myelomA (PANORAMA). PANORAMA 1 is an international, randomized, double-blind, phase III study of panobinostat (or placebo) + bortezomib + dexamethasone. PANORAMA 2 is a single-arm, open-label, phase II study in bortezomib-refractory patients conducted in the United States. Preliminary response data from PANORAMA 2 were available in 20 patients, and met the predefined threshold allowing, together with early tolerability data, continuation and completion of study enrollment (Schlossman et al, EHA 2011, abstract 0900). Here we present the preliminary demographic and blinded safety results of the phase III study (PANORAMA 1) in patients with relapsed MM. Methods: A total of 672 patients with relapsed or relapsed and refractory MM (1–3 prior lines of therapy) will be enrolled to the trial. Patients with prior bortezomib-based therapy are eligible; however, patients with bortezomib-refractory MM (not achieving at least a minimal response or progressed on or within 60 days of the last bortezomib-containing regimen) are excluded from this trial. PANORAMA 1 comprises 2 treatment phases. Treatment phase 1 consists of eight 3-week cycles of panobinostat (oral 20 mg) or placebo administered thrice weekly and bortezomib (intravenous 1.3 mg/m2) administered twice weekly, each for 2 of 3 weeks. Dexamethasone (oral 20 mg) is administered on the days of and after bortezomib dosing. If clinical benefit is observed, patients proceed to treatment phase 2, which consists of four 6-week cycles with a modified (once-weekly) bortezomib schedule. The primary endpoint is progression-free survival, and the key secondary endpoint is overall survival. Results: Blinded data from 273 enrolled patients in a planned safety analysis are available (data cutoff 31 January 2011). Median age was 64 years (range 32–79 years), and 45% of patients were ≥ 65 years of age. Approximately half of the patients (51%) had received 1 prior line of therapy, whereas 49% received 2–3 prior lines of therapy. Most patients (60%) had also received prior stem cell transplantation. Previous treatment included thalidomide (35%), bortezomib (32%), and lenalidomide (14%). Preliminary pooled safety data (blinded) were available in 267 patients who received 1 dose of treatment. The most commonly affected organ class was the gastrointestinal system (all grade, 59% vs grade 3/4, 15.4%), of which diarrhea was most common (all grade, 36% vs grade 3/4, 10%). Other common AEs (all grade vs grade 3/4) were thrombocytopenia (41% vs 29%), anemia (24% vs 10%), fatigue (24% vs 9%), and neutropenia (12% vs 8%). Peripheral neuropathy of any grade was observed in 19% of patients, with grade 3/4 observed in 3% of patients. Conclusions: Panobinostat in combination with bortezomib has shown clinical activity in relapsed and refractory MM patients. Preliminary analysis of pooled safety data (blinded) from the first 267 patients treated in PANORAMA 1 demonstrated no new or unexpected AEs. Updated demographics and safety data for approximately 500 patients will be presented. The results of PANORAMA 1 and PANORAMA 2 will help determine the potential role of panobinostat in the treatment of patients with relapsed and refractory MM. Disclosures: San-Miguel: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yoon:Celgene: Consultancy; NK Bio: Consultancy. Wiktor-Jedrzejczak:Janssen-Cilag Polska: Honoraria; Novartis: Research Funding. Siritanaratkul:Novartis: Research Funding. Dimopoulos:Novartis: Consultancy, Honoraria. Corradini:Celgene: Honoraria; Genzyme: Honoraria. Günther:Novartis: Consultancy, Research Funding; Celgene: Consultancy. Yong:Janssen-Cilag UK: Honoraria. Wroclawska-Swacha:Novartis: Employment. Weber:Novartis: Employment, Equity Ownership. Bourquelot:Novartis: Employment, Equity Ownership. Hou:Novartis: Membership on an entity's Board of Directors or advisory committees. Einsele:Celgene: Consultancy; Janssen-Cilag: Consultancy; Novartis: Consultancy. Moreau:Novartis: Honoraria. Lonial:Millennium: Consultancy; Celgene: Consultancy; Merck: Consultancy; Onyx: Consultancy; BMS: Consultancy; Novartis: Consultancy. Richardson:Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Abstract: Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008–2015 who initiated first‐line therapy (LOT1). Of these patients, 33·9% underwent autologous stem cell transplantation (ASCT). During follow‐up, 501 (45·4%) and 129 (11·7%) patients initiated second‐ (LOT2) and third‐line therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide‐based therapy, from 66·7% to 42·6%, and chemotherapy from, 20·2% to 5·9%, whereas use of bortezomib‐based therapy or bortezomib + thalidomide increased from 10·7% to 45·5%. Bortezomib‐based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non‐ASCT and ASCT patients, median progression‐free survival (PFS) was 15·0 and 31·1 months following LOT1 and 10·9 and 9·5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib‐based or thalidomide‐based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.

Abstract: Objectives: Perforin and granzyme B are essential proteins for protective immune responses mediated by Cytotoxic T Lymphocytes (CTLs) and Natural Killer cells (NK) against cancers, especially those of hematological origin. Our study investigated polymorphisms in the perforin gene (PRF1) and quantified the levels of the perforin and granzyme B proteins in patients with multiple myeloma (MM). Methods: The PRF1 coding region was evaluated in 58 patients with MM and 78 healthy individuals using direct sequencing. Quantitative real-time PCR was performed to quantify gene expression, and flow cytometry was used to determine the intracellular protein levels. Results: We did not observe differences in the allele frequencies of polymorphisms in the PRF1 gene as well as in perforin and granzyme B protein expression between patients with MM and healthy individuals. However, reduced expression of perforin or granzyme B genes was associated with a shorter survival time. In addition, patients with MM had significantly more CTLs expressing perforin and granzyme B, and had an increased number of NK cells. Conclusion: Our study suggests that the gene expression profile of perforin and granzyme B is a potential prognostic marker for MM.

Abstract: CONTEXTO E OBJETIVO: A daunorrubicina lipossomal tem sido usada no tratamento em várias doenças hematológicas malignas, incluindo mieloma múltiplo (MM). O objetivo deste estudo foi avaliar a eficácia, efeitos colaterais e toxicidade da daunorrubicina lipossomal and dexametasona no Protocolo DD. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado nos hospitais Sírio Libanês, São Camilo, Brasil e no Hospital Alemão Oswaldo Cruz. MÉTODOS: 20 pacientes com MM ativo receberam daunoxome (25-30 mg/m²/dia) por três dias consecutivos, mensal, por quatro meses (total de quatro ciclos), e dexametasona, 10 mg a cada seis horas por quatro dias consecutivos (dia 1 - 4, 9 - 12 e 17 - 20), também mensal. RESULTADOS: A mediana entre o diagnóstico e o início do protocolo DD foi de 13 meses. Quinze pacientes receberam alguma quimioterapia anterior ao protocolo DD. Uma redução maior que 50% do pico monoclonal sérico foi observada em seis paciente após o primeiro ciclo do DD (30%), em seis pacientes após o segundo ciclo (30%), em quatro pacientes após o terceiro ciclo (20%) e em quatro pacientes não houve redução (20%). No início do protocolo, 17 pacientes (85%) apresentavam anemia e em 12 destes pacientes (70%) a anemia foi corrigida. Doença progressiva foi observada em três pacientes (15%), um apresentava resposta mínima, quatro pacientes (20%) apresentaram resposta parcial e 12 (60%) apresentaram resposta completa. A toxicidade hematológica foi aceitável.Toxicidade em trato gastrointestinal foi leve, consistindo em náusea (10%) e anorexia (15%), sem episódios de vômito. CONCLUSÃO: Este tratamento apresentou uma baixa toxicidade, uma boa taxa de resposta e pode ser usado previamente ao transplante de medula óssea autogênico.