Abstract Introduction Multiple myeloma is characterized by proliferation of clonal plasma cells. The identification of prognostics factors to identify patient's risk is important. Among the studied factors, it was identified of relevant importance the lactic dehydrogenase. Objectives To evaluate the impact of the value of DHL in combination with the score ISS in the medium patients overall survival (OS). Methods It is a retrospective cohort with 252 patients with MM recently-diagnosed that attendance in the institution of the study. Results To evaluate the association between DHL and ISS, we found 6 new groups to be analyzed: ISS I and normal DHL with medium overall survival not reached, and with DHL loud with medium OS of 69,8 months, ISS II and normal DHL with medium overall survival of 78,8 months and with DHL loud with medium OS of 73,9 months, ISS III and normal DHL with medium overall survival of 46,7 months and with DHL loud with medium OS of 45,5 months. Conclusion Through the association of ISS I and normal DHL, ISS III and high DHL and others combinations, we build a new score with superior impact prognostic in our population treated in real life.

ABSTRACT Extraordinary progress has been made over the last decade in the treatment of multiple myeloma with the incorporation of new drugs, particularly proteasome inhibitors, immunomodulators, and monoclonal antibodies. The combined use of innovative drugs, already in the first lines of treatment, has led to an expressive increase in the survival of these patients. However, the approach to relapse remains a great challenge, and the disease continues to be incurable. In this scenario, modern immunotherapy has gained the limelight, especially with its recent use of CAR-T cells in clinical trials, as in the case of multiple myeloma, having the BCMA as the primary target. The results are impactful in the treatment of multiple myeloma patients who have had multiple relapses and are triple- and penta-refractory. In this Consensus, we have brought together a group of experts in multiple myeloma to discuss and forward their recommendations for the future, which we hope is very near, incorporating the CAR-T in our country.

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

ABSTRACT Background: Bone marrow angiogenesis is increased in multiple myeloma (MM) patients, prompting the rationale for using antiangiogenic drugs in the treatment of these patients. Objective: To assess angiogenesis in patients with MM at diagnosis and following treatment with an antiangiogenic drug. Patients and Methods: Twenty-three patients with newly diagnosed MM were treated with thalidomide-based regimens. Bone marrow evaluation was made before and following treatment and included angiogenesis assessment, which was quantified through microvessel density (MVD) determination, by means of anti-CD34 immunohistochemical labeling, and classified either as high MVD or low MVD, according to the mean CD34 count: above or below the median of 12.6. Results: The pre-therapy median MVD was 12 (7.5-18.3) versus 8.7 (5.35-18.5) post-therapy, p = 0.2114. Conclusions: Our study found no reduction in MVD before and following treatment and, accordingly, we could establish no relationship between MVD and response to therapy in the sample we studied.

Abstract The treatment of patients with relapsed and/or refractory multiple myeloma has improved considerably in the last 15 years, after the introduction of proteasome inhibitors and immunomodulatory drugs. The first clinical trials with new proteasome inhibitors have produced exciting results, particularly those comparing triplet regimens with standard doublet regimens, with a gain in progression-free survival accompanied by an acceptable safety profile and either similar or better health-related quality of life. New proteasome inhibitors hold the potential to fill unmet needs in multiple myeloma management regarding improvement of clinical outcomes, including delayed progression of disease in high-risk patients. This review summarizes the main pharmacological properties and clinical outcomes of these agents, and discusses their potential to change the whole multiple myeloma therapeutic landscape.

Abstract Introduction: The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. Methods: This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Results: Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Conclusion: Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable.

Abstract Background: The emergence of oligoclonal bands, proteins differing from those originally identified at diagnosis, has been reported in multiple myeloma patients after high-dose chemotherapy followed by autologous stem cell transplantation and after successful conventional chemotherapy. The clinical relevance of oligoclonal bands remains unclear, but their emergence has been associated with better prognosis. The aim of the present study was to determine the prevalence, clinical characteristics and prognostic impact of the presence of oligoclonal bands in multiple myeloma patients. Methods: A retrospective cohort study was conducted. The study included newly diagnosed multiple myeloma patients with at least very good partial response after conventional dose or high-dose chemotherapy followed by autologous stem cell transplantation. The emergence of oligoclonal bands was identified using serum protein electrophoresis as well as serum and urine immunofixation techniques. Results: A total of 101 patients were included with a median follow-up of 42 months. In total, 55% were male, and the median age was 58 years (29-87 years). Fifty-one (50.5%) patients developed oligoclonal bands. They comprised 60% (45/75) of patients treated with autologous stem cell transplantation and 23% (6/26) of those who were not transplanted. Patients with oligoclonal bands showed better progression-free survival than those without the emergence of oligoclonal bands (p-value = 0.0075). Conclusion: The prevalence of oligoclonal bands in this study population was 50.5% with its frequency being greater in cases treated with autologous stem cell transplantation and in those attaining complete remission. Complete remission was more important than the emergence of oligoclonal bands on progression-free survival.

Abstract The diagnosis of Multiple Myeloma is a challenge to the physician due to the non-specific symptoms (anemia, bone pain and recurrent infections) that are commonplace in the elderly population. However, early diagnosis is associated with less severe disease, including fewer patients presenting with acute renal injury, pathological fractures and severe anemia. Since 2006, the serum free light chain test Freelite® has been included alongside standard laboratory tests (serum and urine protein electrophoresis, and serum and urine immunofixation) as an aid in the identification of monoclonal proteins, which are a cornerstone for the diagnosis of Multiple Myeloma. The serum free light chain assay recognizes the light chain component of the immunoglobulin in its free form with high sensitivity. Other assays that measure light chains in the free and intact immunoglobulin forms are sensitive, but unfortunately, due to the nomenclature used, these assays (total light chains) are sometimes used in place of the free light chain assay. This paper reviews the available literature comparing the two assays and tries to clarify hypothetical limitations of the total assay to detect Multiple Myeloma. Furthermore, we elaborate on our study comparing the two assays used in 11 Light Chain Multiple Myeloma patients at presentation and 103 patients taken through the course of their disease. The aim of this article is to provide a clear discrimination between the two assays and to provide information to physicians and laboratory technicians so that they can utilize the International Myeloma Working Group guidelines.

Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study).The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1%) and in the thalidomide and dexamethasone group (59.2%) than in the vincristine, doxorubicin, and dexamethasone group (16.2%). The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line induction therapy in the Brazilian public health system.

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.

CONTEXT AND OBJECTIVE: Liposomal daunorubicin has been used to treat hematological malignancies, including multiple myeloma (MM). The goal was to evaluate efficacy, side-effects and toxicity of liposomal daunorubicin and dexamethasone ("DD Protocol"). DESIGN AND SETTING: Prospective study at Sírio-Libanês, São Camilo, Brasil and Alemão Oswaldo Cruz hospitals. METHODS: Twenty consecutive patients with active MM received four cycles of liposomal daunorubicin intravenously for two hours (25-30 mg/m²/day) on three consecutive days per month, with oral dexamethasone (10 mg every six hours) on four consecutive days three times a month. RESULTS: The male/female ratio was 1:1 and median age 60. Nine patients were stage IIA, ten IIIA and one IIIB. The median from diagnosis to starting DD was 13 months. All patients received four cycles, except one. Fifteen had already received chemotherapy before DD. Responses of > 50% reduction in serum monoclonal paraprotein were observed in six patients after first cycle (30%), six after second (30%) and four after third (20%), while four (20%) did not obtain this. Initially, 17 patients (85%) had anemia: 12 (70%) achieved correction. Progressive disease was observed in three patients (15%), while one had minimal response, four (20%) partial and 12 (60%) complete. Hematological toxicity was acceptable: three patients (15%) had neutrophils < 1,000/mm³; none had thrombocytopenia. Gastrointestinal toxicity was mild: nausea (10%), anorexia (15%) and no vomiting. CONCLUSIONS: This treatment has mild toxicity and good response rate. It may therefore be feasible before autologous bone marrow transplantation.

O mieloma múltiplo consiste na proliferação de células plasmáticas. Raramente apresenta, ao diagnóstico, morfologia de células imaturas com citoplasma amplo basofílico, sugerindo quadro leucêmico inicial. O objetivo deste artigo é mostrar a importância da imunofenotipagem na elucidação destes achados morfológicos pela expressão simultânea de antígenos plasmocíticos, mielomonocíticos e de linhagem linfóide T, confirmando a hipótese diagnóstica de mieloma mielomonocítico. Apresentamos dois casos de mieloma mielomonocítico através de análise morfológica (coloração pancromática de Romanovsky), citoquímica (PAS, peroxidase, sudan black, alfanaftil acetato esterase e oil red), citogenética e imunofenotipagem por citometria de fluxo em sangue periférico e medula óssea, de acordo com as técnicas recomendadas. Foram utilizados os anticorpos monoclonais: CD2, CD3, CD4, CD5, CD7, CD10, CD13, CD15, CD19, CD20, CD25, CD33, CD34, CD38, CD45, CD56, CD71, HLA-DR, TCR alfa/beta, TCR gama/delta, kappa, lambda, IgM e IgD de superfície e intracitoplasmática, assim como MPO, CD79a e CD3 intracitoplasmático. Utilizamos as técnicas de banda G e FISH nas análises citogenéticas. Foram observadas alterações clonais em ambos os casos, sendo uma com trissomia do cromossomo 8 e outro caso com deleção do braço longo do cromossomo 7 e do braço curto do cromossomo 6. Os percentuais de positividade encontrados nos anticorpos monoclonais CD4, CD7, CD10, CD13, CD14, CD15, CD33, CD38 e CD56 de forte expressão, HLA-DR, TCR gama/delta, MPO e IgM intracitoplasmático no histograma de volume x complexidade e no histograma de CD45 x complexidade permitiram concluir este diagnóstico em ambos os casos, demonstrando a importância do método.

Multiple myeloma is a malignant disease caused by unregulated proliferation of mature plasma cells. Very few cases present as blast cells in the bone marrow with intense basophylic cytoplasm and monocytoid morphology, suggesting acute leukemia. This paper presents immonophenotypying in 2 cases with the diagnostic hypoteses of myelomonocytic myeloma, showing the simultaneous expression of plasmocytic, myelomonocytic and T cell antigens. Immonophenotypying was done in peripheral blood and bone marrow with classical techniques, using the following monoclonal antibodies: CD2, CD3, CD4, CD5, CD7, CD10, CD19, CD20, CD25, CD33, CD34, CD38, CD41, CD45, CD56, CD71, HLA-DR, TCR alpha/beta, DCR gama/delta, kappa, lambda, surface IGM and IGG, intracitoplasmic kappa, lambda, IGM and IGD, MPO, CD79a and intracitoplasmic CD3. Morphology was evaluated with pan-chromatic Romanovsky stain and cytochemical stains - PAS, peroxidase, Sudan Black B, alpha-naphtil acetate esterase and Oil Red O. Cytogenetic analysis was done with banding techniques and FISH. Clonal cytogenetic alterations were present in both cases, one with chromosomo 8 trysomy and the other with long arm delection of chromosome 7 and short arm delection of chromosome 6. The percentage positivity of specific markers were clean cut making the diagnosis clear.