Daratumumabe em combinação com bortezomibe e dexametasona para o tratamento de pacientes com mieloma múltiplo recidivado e/ou refratário que receberam uma única terapia prévia no Sistema Único de Saúde (SUS) / Daratumumab in combination with bortezomib and dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma who have received a single prior therapy in the Unified Health System (SUS)

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

The prognostic effect on childhood acute lymphoblastic leukemia of CD34+CD38- expressed in leukemia cells.

OBJECTIVE: Acute lymphoblastic leukemia is the most common malignant disease in children. CD34 and CD38 are expressed in both normal and leukemia cells, but studies of their prognostic associations in childhood acute lymphoblastic leukemia are limited. The aim of this study was to investigate the prognostic effect of CD34 + CD38- leukemia cells in this childhood cancer. METHODS: From January 2014 to January 2019, children with newly diagnosed acute lymphoblastic leukemia were included in this study and followed up until July 2020. The participants were divided into CD34+ and CD34- groups according to CD34 expression level at diagnosis, and the CD34+ group was further divided into CD34 + CD38- and CD34 + CD38+ subgroups based on CD38 expression level. We tracked clinical biological features, therapeutic outcomes, and other patient data for comparisons. RESULTS: The OS and EFS did not differ significantly between the CD34+ and CD34- groups (both P > 0.05). CD34+CD38- group and CD34+CD38+ group were further compared. OS differed significantly between these two groups (χ2 = 3.89, P = 0.048), as did the recurrence rate (χ2 = 5.04, P = 0.025), but EFS did not (χ2 = 1.45, P > 0.05). Survival analysis in patients with recurrence showed a significantly higher OS for the CD34 + CD38+ group compared with the CD34 + CD38- group (χ2 = 5.08, P = 0.024). The CD34+CD38- group and CD34+CD38+ group were matched for propensity scores. When recurrence was compared in the two groups after matching, the difference was statistically significant (P < 0.001). CONCLUSION: CD34+ and CD34- expression does not differ by prognosis in children with acute lymphoblastic leukemia, but CD34 + CD38- may indicate a poor prognosis.

Anti CD38 monoclonal antibodies for multiple myeloma treatment.

CD38 is a transmembrane glycoprotein with ectoenzymatic activity and is highly and uniformly expressed on multiple myeloma (MM) cells. CD38 is expressed also at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. The specificity of this target has increased interest in new drugs and triggered the development of the CD38 monoclonal antibodies Daratumumab (fully human) and Isatuximab (chimeric). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38+ immune-suppressor cells. Monoclonal antibody-based therapy has revolutionized MM therapy in the latest years increasing depth of response. This product review will focus on anti-CD38 monoclonal antibodies Daratumumab and Isatuximab efficacy, safety, pharmacokinetic and pharmacodynamic data from clinical trials.

Daratumumab: A review of current indications and future directions.

Daratumumab, a human IgG1 kappa monoclonal antibody targeting CD38 has transformed the treatment paradigm of multiple myeloma (MM). With the identification of CD38 as a crucial receptor involved in immune system function, it became an ideal target for monoclonal antibody (mAb) drug development in MM. Daratumumab's unique multifaceted mechanism of action has led to great success in the treatment of relapsed refractory multiple myeloma (RRMM) as well as newly diagnosed multiple myeloma (NDMM) patients. Along with its efficacy comes a low toxicity profile, improved further with the introduction of subcutaneous daratumumab. With such success within MM, daratumumab is now being explored in other disease states. This article will review daratumumab's drug development, practical use, and future potential indications.

CD38 at the junction between prognostic marker and therapeutic target.

CD38 is an ectoenzyme involved in transmembrane signaling and cell adhesion and is used as a disease marker for leukemias and myeloma. CD38 is a dependable negative prognostic marker for chronic lymphocytic leukemia (CLL). Recent evidence indicates that CD38 is a component of a complex network delivering growth and survival signals to CLL cells. In conjunction with chemokines and their receptors, CD38 also influences cell migratory responses. These considerations are the rationale for devising a CLL therapy that uses CD38 as the target. The use of reagents specifically blocking the molecule might provide a new approach for interfering with deleterious growth circuits, therefore increasing the susceptibility of leukemic cells to conventional chemotherapy.