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INTRODUCCIÓN: Cuadro clínico: El mieloma múltiple (MM) produce diversas manifestaciones clínicas como lesiones y fracturas óseas, insuficiencia renal, hipercalcemia, infecciones recurrentes y/o anemia. Esta condición representa uno de los cánceres hematológicos más frecuentes, con una incidencia estandarizada por edad de 1.92 por cada cien mil personas a nivel mundial. En Perú, el MM es el tercer cáncer hematológico más frecuente y con mayor mortalidad. Asimismo, se estima responsable de la pérdida de 5365 años de vida saludable al año, principalmente por su componente de muerte prematura. Tecnología sanitária: El daratumumab es un anticuerpo monoclonal que se une a la proteína CD38, expresada en alto nivel en las células tumorales del MM. Se encuentra indicado para uso combinado con bortezomib y dexametasona (D-Vd) en pacientes con MM tratados con al menos una línea de terapia previa. La dosis recomendada es 16 mg/kg de peso, administrados en ciclos semanales durante las primeras nueve semanas, cada tres semanas entre las semanas 10 y 24, y cada cuatro semanas a pa

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ABSTRACT: The total therapy (TT) IIIB phase 2 study incorporated bortezomib into tandem melphalan-based hematopoietic stem cell transplantation with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide for induction/consolidation and bortezomib, lenalidomide, and dexamethasone (VRD) for maintenance in patients with newly diagnosed multiple myeloma (MM). This updated analysis presents a 15.4-year median follow-up. Of 177 patients, 21% patients had gene expression profile (GEP)-defined high-risk MM. 15-year progression free survival (PFS) was 27.9%. Median PFS was better in GEP-defined low-risk patients at 7.8 years and in International Staging System stage 1 patients at 8.7 years. Overall, median OS was 9.1 years, and 15-year overall survival (OS) was 35.9%. GEP-defined low-risk patients' median OS was 11.2 years, and that of GEP-defined high-risk patients was 2.8 years. There was no difference in OS between TT IIIB and TT IIIA. This study includes the longest follow-up of patients treated with maintenance VRD reported to date. In patients with GEP-defined low-risk, nearly half and one-third of patients without ongoing treatment showed no signs of progression at 10 and 15 years, respectively. One-third of patients survived more than 15 years, but 3 years of VRD maintenance did not improve outcomes for patients with GEP-defined high-risk MM. The study was registered on www.clinicaltrials.gov as #NCT00572169.

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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.

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Background: Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan dysfunction. Limited data exist on the clinical features of AL amyloidosis. Objective: This study aims to describe the clinical characteristics, treatments, and outcomes in Colombian patients with AL amyloidosis. Methods: A retrospective descriptive study was conducted at three high-complexity centers in Medellín, Colombia. Adults with AL amyloidosis diagnosed between 2012 and 2022 were included. Clinical, laboratory, histological, treatment, and survival data were analyzed. Results: The study included 63 patients. Renal involvement was most prevalent (66%), followed by cardiac involvement (61%). Multiorgan involvement occurred in 61% of patients. Amyloid deposition was most commonly detected in renal biopsy (40%). Bortezomib-based therapy was used in 68%, and 23.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). Hematological response was observed in 95% of patients with available data. Cardiac and renal organ responses were 15% and 14%, respectively. Median overall survival was 45.1 months (95% CI: 22.2-63.8). In multivariate analysis, cardiac involvement was significantly associated with inferior overall survival (HR 3.27; 95% CI: 1.23-8.73; p=0.018), HDCT-ASCT had a non-significant trend towards improved overall survival (HR 0.25; 95% CI: 0.06-1.09; p=0.065). Conclusions: In this study of Colombian patients with AL amyloidosis, renal involvement was more frequent than cardiac involvement. Overall survival and multiorgan involvement were consistent with data from other regions of the world. Multivariate analysis identified cardiac involvement and HDCT-AHCT as possible prognostic factors.

Antecedentes: La amiloidosis por amiloide de cadenas ligeras (AL) se caracteriza por el depósito de fibrillas amiloides derivadas de cadenas ligeras de inmunoglobulinas monoclonales, lo que resulta en disfunción multiorgánica. Existen datos limitados sobre las características clínicas de la amiloidosis AL. Objetivo: Este estudio tiene como objetivo describir las características clínicas, tratamientos y desenlaces en pacientes colombianos con amiloidosis AL. Métodos: Se llevó a cabo un estudio descriptivo retrospectivo en tres centros de alta complejidad en Medellín, Colombia. Se incluyeron adultos con diagnóstico de amiloidosis AL entre 2012 y 2022. Se analizaron datos clínicos, de laboratorio, histológicos, de tratamiento y de supervivencia. Resultados: El estudio incluyó 63 pacientes. La afectación renal fue más prevalente (66%), seguida de la afectación cardíaca (61%). El 61% de los pacientes presentaron afectación multiorgánica. El depósito amiloide se detectó con mayor frecuencia en la biopsia renal (40%). El tratamiento basado en bortezomib se utilizó en el 68%, y el 23.8% recibió altas dosis de quimioterapia con trasplante autólogo de progenitores hematopoyéticos (ADQT-TAPH). Se observó respuesta hematológica en el 95% de los pacientes con datos disponibles. La respuesta de órgano cardíaca y renal fue del 15% y 14%, respectivamente. La mediana de la supervivencia global fue de 45.1 meses (IC del 95%: 22.2-63.8). En el análisis multivariado, la afectación cardíaca se asoció significativamente con una supervivencia global inferior (HR 3.27; IC del 95%: 1.23-8.73; p=0.018), ADQT-TAPH mostró una tendencia no significativa hacia una mejora en la supervivencia global (HR 0.25; IC 95%: 0.06-1.09; p=0.065). Conclusiones: En este estudio de pacientes colombianos con amiloidosis AL, la afectación renal fue más frecuente que la afectación cardíaca. La supervivencia global y la afectación multiorgánica fueron consistentes con datos de otras regiones del mundo. El análisis multivariado identificó la afectación cardíaca y ADQT-TAPH como posibles factores pronósticos.

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Light chain amyloidosis (AL) is a rare and underdiagnosed disease. The best treatment available is autologous bone marrow transplantation (BMT). Cardiac involvement is the main prognostic determinant in this pathology and sometimes an impediment to receive BMT. We present a clinical case of a 44-year-old who consulted for signs and symptoms of heart failure (HF) with elevated cardiac biomarkers. A transthoracic echocardiogram showed increased wall thickness with global hypokinesia and mildly impaired ejection fraction (50%). The patient was admitted to the coronary unit for treatment with diuretics and for etiological study of the condition. In view of the suspicion of infiltrative disease, a bone scintigraphy with pyrophosphate and free light chains in serum were requested. The bone scintigraphy was not suggestive of transthyretin amyloidosis and the free light chains showed a ratio of less than 0.26 with lambda predominance. A gum biopsy was performed and confirmed the diagnosis of AL amyloidosis. After diagnosis, specific chemotherapy treatment with Cyclophosphamide, Bortezomib and Dexamethasone (CYBORD scheme) and Daratumumab was started. He evolved with refractory HF so it was decided to admit him to the cardiac transplantation list, receiving the same soon after, with good evolution. This allowed the patient to restart the chemotherapy regimen and finally receive BMT, with good evolution.

La amiloidosis por depósito de cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuente y subdiagnosticada. El mejor tratamiento disponible al momento es el trasplante autólogo de médula ósea (TMO). El compromiso cardíaco es el principal determinante pronóstico en esta patología y en ocasiones un impedimento para recibir el TMO. Se presenta el caso de un varón de 44 años que consultó por signos y síntomas de insuficiencia cardiaca (IC) con biomarcadores cardiacos elevados. Se realizó un ecocardiograma transtorácico donde se objetivó aumento de espesores parietales con hipoquinesia global y fracción de eyección deteriorada en grado leve (50%). El paciente se internó en unidad coronaria para balance negativo y para estudio etiológico del cuadro. Ante la sospecha de enfermedad infiltrativa, se solicitaron un centellograma óseo con pirofosfato y cadenas livianas libres en suero. El centellograma óseo resultó no sugestivo para amiloidosis por transtiretina y las cadenas livianas libres mostraron una relación menor a 0.26 con predominio lambda. Se realizó una biopsia de encía que confirmó el diagnóstico de amiloidosis AL. Posterior al diagnóstico comenzó tratamiento quimioterápico específico con Ciclofosfamida, Bortezomib y Dexametasona (esquema CYBORD) y Daratumumab. Evolucionó con IC refractaria por lo que ingresó a lista de trasplante cardiaco, recibiendo el mismo al poco tiempo con buena evolución. Esto permitió reiniciar el esquema quimioterápico y en segundo término finalmente recibir el TMO, con buena evolución.

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INTRODUÇÃO: O mieloma múltiplo (MM) é uma neoplasia maligna, caracterizada pela proliferação desregulada de plasmócitos (responsáveis pela produção de anticorpos), resultando principalmente em produção exacerbada de imunoglobulina não funcional. As manifestações clínicas mais comuns são dores ósseas e fraturas, anemia, insuficiência renal e infecções recorrentes. É a segunda neoplasia hematológica mais frequente (10-15% dos casos) e representa 1% de todos os tumores malignos, sendo considerada uma doença progressiva e sem cura, com a maioria dos pacientes apresentando múltiplas remissões e recidivas. O manejo terapêutico de MM recidivado e /ou refratário (MMRR) ainda é um desafio devido ao aumento da resistência às terapias, piora do prognóstico e declínio da qualidade de vida desses pacientes conforme progridem nas linhas de tratamento. HISTÓRICO DE RECOMENDAÇÕES DA CONITEC: Em fevereiro de 2022 foi publicado o Relatório de Recomendação nº 702 analisando o uso de daratumumabe para o controle do MMRR. A recomendação da Conitec e decisão do Ministério da Saúde foi pela não incorporação no SUS, considerando os indicadores de eficiência apresentados e a estimativa elevada de impacto orçamentário. Diferente da demanda de 2022, a solicitação atual, propõe o uso de daratumumabe em associação com bortezomibe e dexametasona apenas para pacientes com MMRR que receberam uma única terapia prévia. PE

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Several studies have shown that diverse components of the bone marrow (BM) microenvironment play a central role in the progression, pathophysiology, and drug resistance in multiple myeloma (MM). In particular, the dynamic interaction between BM mesenchymal stem cells (BM-MSC) and MM cells has shown great relevance. Here we showed that inhibiting both PKC and NF-κB signalling pathways in BM-MSC reduced cell survival in the MM cell line H929 and increased its susceptibility to the proteasome inhibitor bortezomib. PKC-mediated cell survival inhibition and bortezomib susceptibility induction were better performed by the chimeric peptide HKPS than by the classical enzastaurin inhibitor, probably due to its greatest ability to inhibit cell adhesion and its increased capability to counteract the NF-κB-related signalling molecules increased by the co-cultivation of BM-MSC with H929 cells. Thus, inhibiting two coupled signalling molecules in BM-MSC was more effective in blocking the supportive cues emerging from the mesenchymal stroma. Considering that H929 cells were also directly susceptible to PKC and NF-κB inhibition, we showed that treatment of co-cultures with the HKPS peptide and BAY11-7082, followed by bortezomib, increased H929 cell death. Therefore, targeting simultaneously connected signalling elements of BM-MSC responsible for MM cells support with compounds that also have anti-MM activity can be an improved treatment strategy.

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Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder that can precede the diagnosis of multiple myeloma. MGUS is characterized by the presence of a monoclonal paraprotein without evidence of multiple myeloma or other lymphoplasmacytic malignancies. Even though MGUS is an asymptomatic condition that does not require management strategies other than periodic follow-up to prevent complications, secondary nonmalignant diseases may arise, requiring control of the plasma cell clone. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that occurs in patients with no prior personal or family history of bleeding. It is associated with several other disorders, such as neoplasia, mainly hematological (including MGUS and other lymphoproliferative disorders), autoimmune, infectious and cardiac diseases. At diagnosis, patients usually present with cutaneous and mucosal bleeding, including gastrointestinal bleeding. Here, we report a case of a patient with MGUS who developed AVWS after one year of follow-up. The patient was refractory to glucocorticoids and cyclophosphamide and achieved remission only after monoclonal paraprotein was eradicated following treatment with bortezomib and dexamethasone. Our report sdemonstrates that, for refractory cases, eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS.

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Primary plasma cell leukemia (pPCL) is an infrequent and aggressive plasma cell disorder. The prognosis is still very poor, and the optimal treatment remains to be established. A retrospective, multicentric, international observational study was performed. Patients from 9 countries of Latin America (LATAM) with a diagnosis of pPCL between 2012 and 2020 were included. 72 patients were included. Treatment was based on thalidomide in 15%, proteasome inhibitors (PI)-based triplets in 38% and chemotherapy plus IMIDs and/or PI in 29%. The mortality rate at 3 months was 30%. The median overall survival (OS) was 18 months. In the multivariate analysis, frontline PI-based triplets, chemotherapy plus IMIDs and/or PI therapy, and maintenance were independent factors of better OS. In conclusion, the OS of pPCL is still poor in LATAM, with high early mortality. PI triplets, chemotherapy plus IMIDs, and/or PI and maintenance therapy were associated with improved survival.

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Light chain (AL) amyloidosis is a form of systemic amyloidosis, causing organ dysfunction, mainly affecting the heart and kidney. Patient-tailored and risk-adapted decision making is critical in AL amyloidosis management. There is limited real-world evidence data from Argentina and Latin America regarding the treatment approaches for AL amyloidosis. This retrospective cohort study aimed to describe the treatment patterns and outcomes in adult patients (>18 years) diagnosed with AL amyloidosis at the Hospital Italiano in Buenos Aires, Argentina, using a 10-yearfollow-up data (June 1, 2010 to May 31, 2019) from the institutional registry of amyloidosis (IRA). The study population had a mean age of 63 years and 54.4% weremale. Heart and kidney were the most frequently affected organs. Of the 90 eligible patients included in the study, 70underwent treatment. Bortezomib-based regimen was the preferred first-line treatment (75.7% patients). Overall,54.4% of the patients presented a deep response (complete or very good partial response). Median overall survival (OS) was 5years, the 1-year OS and progression free survival rates were 80% (95% confidence interval [CI]: 68-87) and 80% (95%CI 68-87)), respectively. This study provides vital real-world evidence for the long-term treatment patterns and survival in a large cohort of AL amyloidosis patients in Argentina.

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BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. AIM: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. RESULTS: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

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INTRODUCTION: Immunoglobulin light chain (AL) amyloidosis is a rare disease. Treatment is challenging, justified in part by systemic compromise and limited scientific evidence. OBJECTIVES: Develop evidencebased recommendations that allow adequate treatment of patients with amyloidosis AL. METHODS: A list of PICO format questions focused on the effectiveness and safety of amyloidosis AL treatment was generated. PubMed, Cochrane and Epistemonikos were searched. The levels of evidence and grades of recommendation were based on the GRADE system. RESULTS: 11 recommendations were generated. In selected patients with amyloidosis AL, autologous hematopoietic stem cell transplantation (ASCT) is recommended after induction with bortezomibbased regimens and conditioning with melphalan, since it could deepen the hematological and organ response, its durability and improve survival. In patients not eligible for ASCT, first-line treatment with bortezomib-based regimens is recommended, since it is likely to achieve a higher rate of hematological and organ response and improve survival. In patients with a contraindication or inaccessibility to bortezomib, treatment with alkylating agents and corticosteroids is recommended, since they are likely to achieve haematological and organ response and improve survival. DISCUSSION: These treatment recommendations are based on the available evidence and the experience of the panel of experts, in a scenario of limited available resources, according to developing countries.

Introducción: La amiloidosis por cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuente. El tratamiento implica un desafío, justificado en parte por el compromiso sistémico y la evidencia científica escasa. Objetivos: Elaborar recomendaciones basadas en la evidencia que permitan realizar un adecuado tratamiento de pacientes con amiloidosis AL. Métodos: Se generó un listado de preguntas con formato PICO centradas en la efectividad y seguridad del tratamiento de la amiloidosis AL. Se realizó la búsqueda en PubMed, Cochrane y Epistemonikos. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE. Resultados: Se generaron 11 recomendaciones. En pacientes con amiloidosis AL seleccionados, se recomienda el trasplante autólogo de células progenitoras hematopoyéticas (TCPH) posterior a una inducción con esquemas basados en bortezomib y el acondicionamiento con melfalán, ya que podría profundizar la respuesta hematológica, de órgano, su durabilidad y mejorar la supervivencia. En pacientes no elegibles para TCPH, se recomienda el tratamiento de primera línea con esquemas basados en bortezomib, dado que es probable que logre mayor tasa de respuesta hematológica, de órgano y mejore la supervivencia. En pacientes con contraindicación o inaccesibilidad al bortezomib, se recomienda el tratamiento con agentes alquilantes y corticoides, dado que es probable que logren la respuesta hematológica, de órgano y mejoren la supervivencia. Discusión: Estas recomendaciones de tratamiento se basan en la evidencia disponible y la experiencia del panel de expertos, en un escenario de recursos disponibles limitados, acorde a los países en vías de desarrollo.

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INTRODUCTION: Multiple myeloma (MM) is an incurable malignant neoplasm that accounts for approximately 1% of all cancers and 10% of haematological malignancies. Bortezomib is one of the most commonly used medications in first-line treatment and subsequent relapses, either as a single agent or in combination with other therapies. This study aims to assess the effects of bortezomib on the overall survival (OS), progression-free survival, overall response rate, time to next treatment, health-related quality of life, compliance, adverse events and treatment-related death in patients with MM. METHODS AND ANALYSIS: We have performed a systematic review and meta-analysis and will include both randomised and non-randomised controlled studies where the effect of bortezomib was compared in similar or dissimilar background therapies in each arm. General and adaptive search strategies have been created for the following electronic health databases: Embase, Medline, LILACS and CENTRAL. Two reviewers have independently selected eligible studies, will assess the risk of bias, and will extract data from the included studies. Similar outcomes will be plotted in the meta-analysis using the Stata Statistical Software V.17. The relative risk will be calculated with a 95% CI as the effect size of bortezomib. For the OS and progression-free survival, we calculate the overall OR from the HRs of each included study. Peto's one-step OR will be calculated for event rates below 1%. We will use the Grading of Recommendations Assessment, Development and Evaluation system to evaluate the certainty of evidence. ETHICS AND DISSEMINATION: As no primary data collection will be undertaken, formal ethical assessment is not required. We plan to present the results of this systematic review in a peer-reviewed scientific journal, conferences and popular press. PROSPERO REGISTRATION NUMBER: CRD42020151142.

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Multiple Myeloma (MM) is characterized by a clonal expansion of plasma cells in the bone marrow. These cells typically produce a monoclonal immunoglobulin, and its symptoms arise either from plasma cell infiltration in several organs, or secondary to the presence of a monoclonal protein peak. Symptoms can be summarized by the acronym CRAB (hypercalcemia, renal failure, anemia and bone lesions). Sometimes, in the setting of a protein secreting monoclonal gammopathy, formation of cryoglobulins develops. Cryoglobulins are plasma proteins that precipitate at low temperatures, forming a cold - induced precipitate at small vessels, causing a wide range of clinical manifestations. We report a female consulting for ulcers lasting 2 months in the left foot associated with purpuric lesions in both lower limbs. Protein electrophoresis showed a monoclonal peak in the gamma region. Bone marrow aspirate showed 27% of plasma cells with kappa chain restriction by cytometry. The presence of cryoglobulins was confirmed. The patient was treated with dexamethasone and bortezomib, with a progressive healing of lower limb lesions and disappearance of cryoglobulins. She was discharged in good conditions.

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Immunoglobulin light chain (AL) amyloidosis is a rare disease. Treatment is challenging, justified in part by systemic compromise and limited scientific evidence. Develop evidencebased recommendations that allow adequate treatment of patients with amyloidosis AL. A list of PICO format questions focused on the effectiveness and safety of amyloidosis AL treatment was generated. PubMed, Cochrane and Epistemonikos were searched. The levels of evidence and grades of recommendation were based on the GRADE system.11 recommendations were generated. In selected patients with amyloidosis AL, autologous hematopoietic stem cell transplantation (ASCT) is recommended after induction with bortezomibbased regimens and conditioning with melphalan, since it could deepen the hematological and organ response, its durability and improve survival. In patients not eligible for ASCT, first-line treatment with bortezomib-based regimens is recommended, since it is likely to achieve a higher rate of hematological and organ response and improve survival. In patients with a contraindication or inaccessibility to bortezomib, treatment with alkylating agents and corticosteroids is recommended, since they are likely to achieve haematological and organ response and improve survival. These treatment recommendations are based on the available evidence and the experience of the panel of experts, in a scenario of limited available resources, according to developing countries.

La amiloidosis por cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuente. El tratamiento implica un desafío, justificado en parte por el compromiso sistémico y la evidencia científica escasa. Objetivos: Elaborar recomendaciones basadas en la evidencia que permitan realizar un adecuado tratamiento de pacientes con amiloidosis AL. Métodos: Se generó un listado de preguntas con formato PICO centradas en la efectividad y seguridad del tratamiento de la amiloidosis AL. Se realizó la búsqueda en PubMed, Cochrane y Epistemonikos. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE. Resultados: Se generaron 11 recomendaciones. En pacientes con amiloidosis AL seleccionados, se recomienda el trasplante autólogo de células progenitoras hematopoyéticas (TCPH) posterior a una inducción con esquemas basados en bortezomib y el acondicionamiento con melfalán, ya que podría profundizar la respuesta hematológica, de órgano, su durabilidad y mejorar la supervivencia. En pacientes no elegibles para TCPH, se recomienda el tratamiento de primera línea con esquemas basados en bortezomib, dado que es probable que logre mayor tasa de respuesta hematológica, de órgano y mejore la supervivencia. En pacientes con contraindicación o inaccesibilidad al bortezomib, se recomienda el tratamiento con agentes alquilantes y corticoides, dado que es probable que logren la respuesta hematológica, de órgano y mejoren la supervivencia. Discusión: Estas recomendaciones de tratamiento se basan en la evidencia disponible y la experiencia del panel de expertos, en un escenario de recursos disponibles limitados, acorde a los países en vías de desarrollo.

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BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. Aim: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. Results: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

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BACKGROUND: In this era of target therapies, novel data on the correlation between response endpoints and survival outcomes in multiple myeloma have arisen. OBJECTIVE: To determine the impact of quality of response on clinical outcomes, using first-line treatment, and identify risk factors influencing progression-free survival (PFS) and overall survival (OS) among myeloma patients. DESIGN AND SETTING: Retrospective analysis on myeloma patients who were treated at the Clinic of Hematology and Clinical Immunology, University Clinical Centre, Nis, Serbia, over a four-year period. METHODS: A total of 108 newly diagnosed patients who received first-line therapy consisting of conventional chemotherapy or novel agent-based regimens were included in this analysis. RESULTS: The quality of response to first-line therapy for the whole cohort was classified as follows: complete response (CR) in 19%; very good partial response (VGPR) in 23%; partial response (PR) in 38%; and less than PR for the remaining patients. After a median follow-up of 25.4 months, the three-year PFS and OS for the entire study population were 47% and 70%, respectively. Achievement of CR was the main factor associated with significantly prolonged PFS and OS, in comparison with patients who reached VGPR and PR. Likewise, addition of the new drugs bortezomib and thalidomide to standard chemotherapy led to considerably extended PFS and OS, compared with conventional therapy alone. CONCLUSIONS: This analysis demonstrated that the quality of response after application of first-line treatment using novel agent-based regimens among multiple myeloma patients was a prognostic factor for PFS and OS, which are the most clinically relevant outcomes.

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Abstract BACKGROUND: In this era of target therapies, novel data on the correlation between response endpoints and survival outcomes in multiple myeloma have arisen. OBJECTIVE: To determine the impact of quality of response on clinical outcomes, using first-line treatment, and identify risk factors influencing progression-free survival (PFS) and overall survival (OS) among myeloma patients. DESIGN AND SETTING: Retrospective analysis on myeloma patients who were treated at the Clinic of Hematology and Clinical Immunology, University Clinical Centre, Niš, Serbia, over a four-year period. METHODS: A total of 108 newly diagnosed patients who received first-line therapy consisting of conventional chemotherapy or novel agent-based regimens were included in this analysis. RESULTS: The quality of response to first-line therapy for the whole cohort was classified as follows: complete response (CR) in 19%; very good partial response (VGPR) in 23%; partial response (PR) in 38%; and less than PR for the remaining patients. After a median follow-up of 25.4 months, the three-year PFS and OS for the entire study population were 47% and 70%, respectively. Achievement of CR was the main factor associated with significantly prolonged PFS and OS, in comparison with patients who reached VGPR and PR. Likewise, addition of the new drugs bortezomib and thalidomide to standard chemotherapy led to considerably extended PFS and OS, compared with conventional therapy alone. CONCLUSIONS: This analysis demonstrated that the quality of response after application of first-line treatment using novel agent-based regimens among multiple myeloma patients was a prognostic factor for PFS and OS, which are the most clinically relevant outcomes.

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OBJECTIVE: Multiple myeloma (MM) is an incurable hematological cancer and its treatment is geared to promote better Health-Related Quality of Life (HRQoL). We aimed to assess HRQoL and compare scores between variables on therapeutic regimens and polypharmacy in MM patients. METHODS: This cross-sectional study was performed from April/2019 to February/2020 in Belo Horizonte, Brazil. HRQoL scores were obtained by the QLQ-C30 and QLQ-MY20 instruments. Data were retrieved from interviews and medical records. Therapeutic regimens were grouped into thalidomide-containing regimens; bortezomib-containing regimens; bortezomib and thalidomide-containing regimens; other therapeutic regimens, and remission group. We performed univariate analyses by the Mann-Whitney method and adopted the Kruskal-Wallis test for multiple comparisons. Robust multiple linear regression was used to determine the association between independent variables and the HRQoL scores. RESULTS: The sample included 225 participants and most patients (65.3%) were on active treatment and had worse scores concerning future perspective. Polypharmacy was associated with worse scores on all scales in the univariate analyses. We observed a difference in the global health and body image (p < .05) scales in the multiple comparisons with therapeutic regimens. The global health scale difference was found between groups with other regimens and the remission group (p < .05). The difference between the bortezomib and thalidomide-containing regimens and remission group was not statistically significant (p = .077) in the body image scale. The multiple linear regression maintained the association of polypharmacy with worse HRQoL scores. CONCLUSION: We identified an independent association between HRQoL and polypharmacy in MM patients. However, there was no difference between the evaluated regimens, suggesting they are equivalent in Brazil about HRQoL.

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