ABSTRACT
Multiple myeloma (MM) remains an incurable malignancy originating from plasma cells. Despite significant advances in treatment, relapses remain inevitable, and novel therapies continue to be needed. Teclistamab-cqyv is a first-in-class, bispecific T-cell engager (BiTE) antibody for the treatment of MM. Teclistamab-cqyv activates the immune system by binding to the cluster of differentiation 3 (CD3) receptor expressed on the surface of T cells and to the B-cell maturation antigen (BCMA) expressed on the surface of MM cells and some healthy B-lineage cells. Teclistamab-cqyv has been shown to be effective in a pivotal trial that demonstrated an overall response rate of more than 60% in heavily pretreated patients. Compared with other BCMA-targeted agents, the side effect profile of teclistamab-cqyv suggests a more tolerable option for elderly patients. Teclistamab-cqyv is now approved by the US Food and Drug Administration (FDA) as monotherapy for the treatment of adult patients with relapsed or refractory MM.
ABSTRACT
BACKGROUND: There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8-93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9â m, 95% CI 25.9-73.8â m) and riociguat (49.5â m, 95% CI 17.3-81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty). CONCLUSION: Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.