Epidemiology and risk factors for the development of infectious complications in newly diagnosed multiple myeloma: a multicenter prospective cohort study in Uruguay.

INTRODUCTION: Infections represent a significant cause of morbidity and mortality in patients with multiple myeloma (MM). In Latin America, data on infectious complications in newly diagnosed MM (NDMM) patients are limited. METHODS: We conducted a multicenter, prospective cohort study of patients with NDMM in Uruguay between June 2019 and December 2020. Patients with active disease, on active therapy and who provided written informed consent were included. Elegible patients were followed for 6 months from the time of diagnosis and before proceeding to autologous stem cell transplantation or until death, whichever occurred first. Our primary endpoint was the number of infectious events that required hospitalization for ≥ 24 h. MAIN RESULTS: Of 124 patients with NDMM, 54 (43.5 %) had infectious complications (74 infectious events), the majority (74.3 %) within the first 3 months from diagnosis. The most common sites of infection were urinary (39.2 %) and respiratory tracts (33.8 %). The microbial agent was identified in 60.8 % of patients with Gram-negative bacteria (71.4 %) as the most common pathogen. Viral and fungal infections were infrequent. In the multivariable analysis, the Eastern Cooperative Oncology Group (ECOG) performance status was ≥ 2 (odds ratio [OR], 2.16; 95 % confidence interval [95 %CI], 1.23 - 3.79; p = 0.008) and creatinine ≥ 2 mg/dl (OR, 2.33; 95 %CI, 1.33 - 4.07; p = 0.003) were independent factors associated with bacterial infections. At 6 months, 14 patients (11.3 %) had died, 50 % related to infectious complications. CONCLUSION: Bacterial infections are a substantial cause of hospital admissions and early death in patients with NDMM. Antibiotic prophylaxis should be considered to reduce infectious complications in patients with MM.

Survival Analysis of Newly Diagnosed Multiple Myeloma Patients after Frontline Autologous Stem Cell Transplantation in a Real-Life Setting.

INTRODUCTION: Autologous stem cell transplantation (ASCT) is the standard consolidation option for transplant-eligible patients with multiple myeloma (MM). The aim of this study is to report the overall survival (OS) and progression-free survival (PFS) outcomes after frontline ASCT in newly-diagnosed MM (NDMM) patients in a real-world setting. METHODS: We conducted a retrospective, survival analysis of all NDMM patients included in the MM Uruguayan Registry. RESULTS: We included 151 NDMM patients treated with induction therapy followed by high-dose melphalan and ASCT as consolidation. The median age at diagnosis was 59 years, and the international staging system (ISS) risk groups were ISS-III 32.9%, ISS-II 37.8%, and ISS-I 29.4%. Frontline induction regimens included bortezomib in 61.6% of cases, and maintenance therapy was used in 63.9% of reported cases. With a median follow-up of 42 months, the 36-month OS and PFS for the whole group were 82.4% (95% CI 75.9% to 89.4%) and 63.8% (95% CI 55.6% to 73.3%), respectively, median OS of 98 months and median PFS of 47 months. The 100-month OS and PFS for the entire group were 48.0% (95% CI 34.9% to 66.0%) and 17.3% (95% CI 8.4% to 35.8%), respectively. CONCLUSION: ASCT is a feasible, safe, and potent strategy that provides a prolonged median OS and PFS in NDMM patients. This approach can be implemented in low-income countries.

Patients Age 40 Years and Younger With Multiple Myeloma Have the Same Prognosis as Older Patients: An Analysis of Real-World Patients' Evidence From Latin America.

PURPOSE: Multiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce. PATIENTS AND METHODS: We analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older. RESULTS: There were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival. CONCLUSION: In conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.

Digital Ischemia as an Unusual Manifestation of Hodgkin's Lymphoma.

Digital ischemia is associated with atherosclerotic, thromboembolic, or connective tissue diseases. Less often, it can be related to malignancy. Paraneoplastic vascular acrosyndromes (Raynaud's syndrome, acrocianosis, and acronecrosis) are associated with adenocarcinoma and less frequently with hematological malignancies. We report the case of a 45-year-old male, smoker, with a 10-day history of pain, cyanosis, and progressive digital necrosis in both hands. In the previous four months, he noticed painless mass in the right axillary gap, drenching night sweats, and weight loss. Physical examination at admission highlighted necrotic lesions on the distal phalanges of both hands (except the thumbs), enlarged lymph nodes in right axillary, and right supraclavicular gaps. Arteriography of upper limbs demonstrated a distal stop in all bilateral digital arteries. Digital ischemia was interpreted as a paraneoplastic phenomenon after other common etiologies were ruled out. Amputation of three phalanges was required due to necrosis. Biopsy of axillary nodes demonstrated nodular sclerosis classical Hodgkin's lymphoma (HL). The patient started conventional ABVD protocol (doxorubicin, bleomycin, vinblastine, and dacarbazine). After 6 cycles, he remained asymptomatic and symptoms of digital ischemia were completely resolved. It was concluded that the presence of acral vascular syndromes should alert the physician about the possibility of underlying malignant disease. Prompt investigation and treatment should be rapidly performed to avoid digital sequelae.

Consenso del Grupo de Estudio Latinoamericano de Mieloma Múltiple (MM) GELAMM para el manejo del MM en estado de pandemia SARS-CoV-2 / COVID- 19 / Consensus of the Latin American Study Group on Multiple Myeloma (MM) GELAMM for the management of MM in a state of Pandemic SARS-CoV-2 / COVID-19

Resumen La enfermedad por COVID-19 fue detectada a finales de 2019 en Wuhan, China. Debido a su rápida propagación fue declarada emergencia sanitaria de forma inicial y luego de identificar casos fuera de China con transmisión autóctona y caracterizado por una mortalidad considerablemente alta en países como Italia y España, fue declarada pandemia por la Organización Mundial de la Salud. Se ha evidenciado que los pacientes mayores y con antecedentes de enfermedades crónicas incluido el cáncer desarrollan una enfermedad severa, presentando mayor riesgo de mortalidad por SARS-CoV2/ COVID-19. Lo anterior es por supuesto especialmente importante en el manejo de pacientes con Mieloma Múltiple (MM), generando en el personal Médico nuevos desafíos, oportunidades de mejora y aprendizajes, que aporten al análisis riesgo-beneficio del tratamiento inmunodepresor en este tipo de patologías. El consenso tiene como objetivo brindar orientación sobre el manejo de pacientes con MM en estos momentos donde el profesional de la salud requiere información para llevar a cabo terapias eficientes en el cuidado del paciente.

Abstract COVID-19 disease was detected in late 2019 in Wuhan, China. Due to its rapid spread, it was initially declared a health emergency, but after cases with indigenous transmission were identified outside China, characterized by considerably high mortality in countries such as Italy and Spain, it was declared a pandemic by the World Health Organization. It has been shown that elderly patients with a history of chronic diseases, including cancer, develop a severe disease, presenting a higher risk of mortality from SARS-CoV2 / COVID-19. This becomes especially important in the management of patients with Multiple Myeloma (MM), generating new challenges, opportunities for improvement and learning opportunities in the health professionals, which will contribute to the risk-benefit analysis of immunosuppressive treatment for this type of pathology. The consensus aims to provide guidance for the management of patients with MM in these times when the health professional requires information to deliver efficient therapies in patient care.

Efectividad del tratamiento con bortezomib en pacientes con mieloma múltiple en el Hospital de Clínicas en el período 2009-2016. Montevideo, Uruguay / Effectiveness of bortezomib treatment in patients with multiple myeloma at the Clínicas Hospital between 2009 and 2016. Montevideo, Uruguay

El mieloma múltiple representa la segunda neoplasia hematológica en frecuencia. Es una enfermedad incurable, cuya sobrevida se ha duplicado en los últimos años, vinculado esto a la aparición de nuevos fármacos. Los planes con bortezomib mejoran la respuesta, sobrevida libre de progresión y sobrevida global. En Uruguay, desde 2009, este fármaco tiene cobertura por parte del Fondo Nacional de Recursos. Este estudio tiene como objetivo analizar la efectividad y toxicidad de bortezomib en pacientes con diagnóstico de mieloma múltiple asistidos en el Hospital de Clínicas. Método: estudio observacional, retrospectivo y descriptivo en el que se incluyeron todos los pacientes con diagnóstico de mieloma múltiple que recibieron tratamiento con bortezomib en primera, segunda o tercera línea en el Hospital de Clínicas de Montevideo, Uruguay, desde 2009 a 2016. Resultados: 36 pacientes recibieron bortezomib. El plan más utilizado fue ciclofosfamida-bortezomib-dexametasona. La vía de administración fue subcutánea en 53,8%. La tasa de respuesta global fue de 79,5% (87% en primera línea y 68,8% en segunda o tercera línea). El 47,2% desarrolló polineuropatía y 30,6% citopenias. Con una mediana de seguimiento de 26 meses la sobrevida global fue de 61% y la sobrevida libre de progresión de 35 meses (IC 95%, 22,6-47,4). Conclusión: el tratamiento con bortezomib logró buena tasa de respuesta. La neuropatía fue la toxicidad más frecuente. Bortezomib es un fármaco efectivo y con adecuado perfil de seguridad para el tratamiento del mieloma múltiple en primera, segunda y tercera línea. (AU)

Multiple mieloma represents the secon neoplasis in terms of frequency. It is an incurable disease, whose survival has doubled in recent years with the emergence of new drugs. Plan including bortezomib improve response, progression free survival and global survival. In Uruguay this drig is covered by the National Resources Find (FNR) since 2009. This study aims to analyse the experience of using bortezomib in patients with a diagnosis of multiple myeloma at the Clínicas Hospital. Method: observational, retrospective and descriptive study that included all patients with a diagnosis of multiple myeloma who received bortezomib treatment in the first, second and/or third line at the Clínicas Hospital of Montevideo; Uruguay from 2009 and 2016. Results: 36 patients received bortezomib. The most frequently used plan was cyclophosphamide-bortezomib-dexamethasone, subcutaneously administered in 54% of cases. Global response rate was 79.5% (87% in the first line, 68.8% in the second or third line). 43.6% of patients developed polineuropahty and 28.2 % cytopenia. With a median follow up of 26 months, global survival was 61% and progression free survival was 35 months, (CI 95%, 22.6-47.4). Conclusion: bortezomib treatment achieved a good reponse rate. Neuropathy was the most frequent toxicity. Bortezomib is an effective drug and it has the adequate safety profile to treat MM in the first, second and third line.

O mieloma múltiplo é a segunda neoplasia hematológica mais frequente. É uma doença incurável, cuja sobrevida se duplicou nos últimos anos graças aparecimento de novos fármacos. Os esquemas terapêuticos com bortezomibe melhoram a resposta, sobrevida livre de progressão e a sobrevida global. Desde 2009 no Uruguai este fármaco é parcialmente financiado pelo Fondo Nacional de Recursos (FNR). O objetivo deste estudo é analisar a experiência com o uso de bortezomibe em pacientes com diagnóstico de mieloma múltiplo atendidos no Hospital de Clínicas. Método: estudo observacional, retrospectivo e descritivo; foram incluídos todos os pacientes com diagnóstico de mieloma múltiplo que receberam tratamento com bortezomibe em primeira, segunda e/ou terceira linha no Hospital de Clínicas de Montevidéu Uruguai, de 2009 a 2016. Resultados: 36 pacientes receberam bortezomibe. O esquema mais utilizado foi ciclofosfamida - bortezomibe - dexametasona. Em 54% dos pacientes a vida de administração foi subcutânea. A taxa de resposta global foi de 79,5% (87% em primeira linha e 68,8% em segunda ou terceira linha). 43,6% apresentou polineuropatia e 28,2% citopenias. Com uma mediana de seguimento de 26 meses a sobrevida global foi de 61% e a sobrevida livre de progressão de 35 meses (IC 95%, 22,6-47,4). Conclusão: o tratamento com bortezomibe apresentou uma boa taxa de resposta. A neuropatia foi o efeito tóxico mais frequente. Bortezomibe é um fármaco efetivo e com perfil de seguridade adequado para o tratamento do MM em primeira, segunda e terceira linha.