Roberto Magalhães

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance.

Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow‐up of 27 months, an intention to treat analysis showed a 2‐year progression‐free survival (PFS) of 30% in arm A (95% CI 22–38) and 64% in arm B (95% CI 57–71; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol.

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.

Can dentists detect multiple myeloma through oral manifestations

Objective To review published data on oral manifestations of multiple myeloma. Methods An electronic database search was performed of articles published from 1971 to November 2016 in order to identify studies that reported oral manifestations of patients with multiple myeloma. Case reports and case series with oral manifestations of multiple myeloma in English were included in the study. An additional search was performed of the references of the selected articles. Results Thirty-seven articles that reported 81 patients with oral manifestations of multiple myeloma were selected: 30 case reports (82%) and seven case series (18%). The most common clinical features in the dental cavity were swelling (65.4%), bone pain (33.3%), paresthesia (27.1%) and amyloidosis lesions (11.1%). Osteolytic lesions detected on imaging exams were reported in the majority of the patients (90.1%) as plasmacytomas or ‘punched-out’ lesions. Conclusions Swelling and osteolytic lesions represent the most common clinical and radiographic signs of the jaws relating to multiple myeloma, respectively.

Transplante de células-tronco hematopoéticas em gamopatias monoclonais

O transplante de celulas-tronco hematopoeticas (TCTH) e um procedimento de fundamental importância na estrategia terapeutica das gamopatias monoclonais. No mieloma multiplo, em particular, o TCTH autologo esta indicado como estrategia de primeira linha para pacientes ate 70 anos de idade. Nesta capitulo serao discutidas as indicacoes, estrategias e recomendacoes envolvendo o TCTH em gamopatias monoclonais, amiloidose e POEMS, frutos da Reuniao de Consenso da Sociedade Brasileira de Transplante de Medula Ossea.

O transplante autólogo de células-tronco hematopoéticas no tratamento do Mieloma Múltiplo

High dose chemotherapy followed by autologous stem cell transplantation has been recognized as an important step in the treatment of multiple myeloma. At least two well designed randomized studies showed better outcomes in patients treated with high doses compared to those treated with conventional chemotherapy. Nowadays, autologous stem cell transplantation should be considered for all under 65-year-old patients. Although autologous stem cell transplantation has modified the prognosis of myeloma, almost all patients still relapse some time after a single transplant, and then another therapeutic approach becomes necessary. With the aim of improving the results in the treatment of myeloma, new approaches including tandem stem cell transplantation, maintenance with thalidomide and new drugs such as bortezomib are being tested. Strategies including these approaches and autologous stem cell transplantation may improve the results of the treatment of myeloma in the future.