RESUMO
The R-CHOP immunochemotherapy protocol has been the first-line (1L) standard of care (SOC) for diffuse large B-cell lymphoma (DLBCL) patients for decades and is curative in approximately two-thirds of patients. Numerous randomized phase III trials, most of them in an "R-CHOP ± X" design, failed to further improve outcomes. This was mainly due to increased toxicity, the large proportion of patients not in need of more than R-CHOP, and the extensive molecular heterogeneity of the disease, raising the bar for "one-size-fits-all" concepts. Recently, an R-CHP regimen extended by the anti-CD79b antibody-drug conjugate (ADC) Polatuzumab Vedotin proved superior to R-CHOP in terms of progression-free survival (PFS) in the POLARIX phase III trial. Moreover, a number of targeted agents, especially the Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib, seem to have activity in certain patient subsets in 1L and are currently being tested in front-line regimens. Chimeric antigen receptor (CAR) T-cells, achieving remarkable results in ≥3L scenarios, are being exploited in earlier lines of therapy, while T-cell-engaging bispecific antibodies emerge as conceptual competitors of CAR T-cells. Hence, we present here the findings and lessons learnt from phase III 1L trials and piloting phase II studies in relapsed/refractory (R/R) and 1L settings, and survey chemotherapy-free regimens with respect to their efficacy and future potential in 1L. Novel agents and their mode of action will be discussed in light of the molecular landscape of DLBCL and personalized 1L perspectives for the challenging patient population not cured by the SOC.
Assuntos
COVID-19 , Neoplasias , Humanos , Imunidade Celular , Neoplasias/genética , RNA Mensageiro/genética , SARS-CoV-2RESUMO
Patients with a myeloproliferative neoplasm (MPN) sometimes show a chronic myelomonocytic leukemia (CMML)-like phenotype but, according to the 2016 WHO classification, a documented history of an MPN excludes the diagnosis of CMML. Forty-one patients with an MPN (35 polycythemia vera (PV), 5 primary myelofibrosis, 1 essential thrombocythemia) and a CMML-like phenotype (MPN/CMML) were comprehensively characterized regarding clinical, hematologic, biologic and molecular features. The white blood cell counts in MPN/CMML patients were not different from CMML patients and PV patients. The hemoglobin values and platelet counts of these patients were higher than in CMML but lower than in PV, respectively. MPN/CMML patients showed myelomonocytic skewing, a typical in vitro feature of CMML but not of PV. The mutational landscape of MPN/CMML was not different from JAK2-mutated CMML. In two MPN/CMML patients, development of a CMML-like phenotype was associated with a decrease in the JAK2 V617F allelic burden. Finally, the prognosis of MPN/CMML (median overall survival (OS) 27 months) was more similar to CMML (JAK2-mutated, 28 months; JAK2-nonmutated 29 months) than to PV (186 months). In conclusion, we show that patients with MPN and a CMML-like phenotype share more characteristics with CMML than with PV, which may be relevant for their classification and clinical management.
RESUMO
OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) often coincides with substance abuse and delinquency. A sample of opioid-maintained inmates was assessed for symptoms of ADHD, substance abuse history, types of offense, psychiatric comorbidities, and psychopharmacological treatment using a standardized battery of instruments. METHOD: Adult inmates (n = 133, mean age 35.7 years, 21.8% female) in opioid-maintenance therapy (OMT) were administered the Adult ADHD self-report scale, Wender Utah Rating Scale, Mini International Neuropsychiatric Interview, -European Addiction Severity Index. RESULTS: Fifty percent screened positive for childhood and 17% for adult ADHD, four (3.1%) received ADHD medication. Inmates with ADHD symptom status were significantly younger at first substance abuse, reported more drug overdoses, longer duration of cocaine and prescribed medication abuse and more in- and outpatient treatments (all p < 0.05). For all inmates in OMT a high rate of psychiatric comorbidities was observed (78.9%). CONCLUSION: There is a need for assessment of ADHD and other psychiatric comorbidities in OMT prisoners. Evidence-based treatment should be routinely provided.