Impact of the lactate dehydrogenase in association with the International Staging System prognostic score in multiple myeloma patients treated in real life.

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.

Impact of the lactate dehydrogenase in association with the International Staging System prognostic score in multiple myeloma patients treated in real life

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.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. IV: CAR-T cell therapy for multiple myeloma patients.

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.

Effect of thalidomide on bone marrow angiogenesis in multiple myeloma patients

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 treatmentwith an antiangiogenic drug.Patients and Methods: Twenty-three patients with newly diagnosed MM were treated withthalidomide-based regimens. Bone marrow evaluation was made before and following treat-ment and included angiogenesis assessment, which was quantified through microvesseldensity (MVD) determination, by means of anti-CD34 immunohistochemical labeling, andclassified either as high MVD or low MVD, according to the mean CD34 count: above or belowthe median of 12.6.RESULTS: The pre-therapy median MVD was 12 (7.5­18.3) versus 8.7 (5.35­18.5) 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 inthe sample we studied.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation

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.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation.

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.

Effect of thalidomide on bone marrow angiogenesis in multiple myeloma patients.

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.

New proteasome inhibitors in the treatment of multiple myeloma

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.

New proteasome inhibitors in the treatment of multiple myeloma.

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.

Analysis of Availability and Access of Anti-myeloma Drugs and Impact on the Management of Multiple Myeloma in Latin American Countries.

INTRODUCTION: Latin American countries (LATAMC) represent a large fraction of patients treated for multiple myeloma (MM) worldwide. In order to understand the difficulty of access to anti-myeloma therapy in LATAMC, we designed this study that explores areas involved in the availability of drugs, such as health care systems, approval times, coverage of new agents, old drugs, use of generics, and the first-line treatments. MATERIAL AND METHODS: We collected data from 16 countries in 2015. RESULTS: The majority of LATAMC (88%; n = 14) had mixed public and private coverage, with patients with MM cared for in public institutions. Although bortezomib and lenalidomide were approved in 100% and 73% in LATAMC, these figures did not translate to real-world practice as one-half of the nations reported unequal access to the new agents (thalidomide, bortezomib, and lenalidomide) in both public and private systems. Conversely, cheaper old drugs, represented by melphalan, were not available commercially in 44% (n = 7) of nations. Thus, first-line MM treatments for old and young patients in public practice were triplets with thalidomide-alkylating agent-steroid, whereas in private practice, treatments involved bortezomib-alkylating agent-steroid. An alarming rate of 30% of the nations reported suboptimal regimens (eg, VAD [vincristine, adriamycin, and dexamethasone]) or the impossibility of transplantation. CONCLUSION: Our data indicates that bortezomib and transplant are still an unmet medical necessity in public systems. In the complex puzzle of myeloma drug access in LATAMC, important issues, such as the adjustment of disparities between health systems, the incorporation of new drugs with an economic cost-effectiveness view, and the re-establishment of essential old drugs, can be a platform to the future.

Multiple myeloma and central nervous system involvement: experience of a Brazilian center.

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.

Multiple myeloma and central nervous system involvement: experience of a Brazilian center

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.

For survival, the emergence of oligoclonal bands after multiple myeloma treatment is less important than achieving complete remission

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.

For survival, the emergence of oligoclonal bands after multiple myeloma treatment is less important than achieving complete remission.

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.

Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies

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.