RESUMEN
Chimeric Antigen Receptor T-cell (CAR-T) therapy has transformed the treatment landscape for hematological malignancies, showing high efficacy in patients with relapsed or refractory (R/R) disease and otherwise poor prognosis in the pre-CAR-T era. These therapies have been usually administered in the inpatient setting due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). However, there is a growing interest in the transition to outpatient administration due to multiple reasons. We review available evidence regarding safety and feasibility of outpatient administration of CD19 targeted and BCMA targeted CAR T-cell therapy with an emphasis on the implementation of outpatient CAR-T programs in community-based centers.
Asunto(s)
Inmunoterapia Adoptiva , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Pacientes Ambulatorios , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/inmunología , Receptores Quiméricos de Antígenos/inmunología , Atención Ambulatoria , Síndrome de Liberación de Citoquinas/terapia , Síndrome de Liberación de Citoquinas/etiología , Antígenos CD19/inmunología , Centros Comunitarios de SaludRESUMEN
PURPOSE: To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of asciminib, an oral tyrosine kinase inhibitor (TKI) used as a third-line treatment option for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase. SUMMARY: CML is a rare cancer caused by a chromosomal translocation that forms a fusion of the BCR and ABL1 genes on chromosomes 22 and 9. Until recently, patients for whom first-line treatment options failed were treated with TKIs that bind to the adenosine triphosphate-binding site on BCR-ABL1. However, because of similar mechanisms of action, there continues to be an unmet need in patients for whom at least 2 TKIs have failed or those with a T315I mutation unable to tolerate ponatinib. In October 2021, the Food and Drug Administration approved asciminib (Scemblix), the first TKI specifically targeting the ABL1 myristoyl pocket (STAMP) via allosteric binding, as a third-line option for patients with chronic-phase (CP)-CML. Asciminib received accelerated approval due to meeting its primary endpoint at week 24, demonstrating a major molecular response rate of 25.5% for patients on asciminib compared to 13.2% for those receiving bosutinib. In addition, patients on asciminib achieved a higher rate of complete cytogenetic response at 40.8% compared to a rate of 24.2% for bosutinib. Clinicians prescribing asciminib should monitor for increased levels of pancreatic enzymes, hypertension, cardiovascular toxicity including ischemic and thromboembolic conditions, and decreased numbers of neutrophils and platelets, as these may require treatment interruption, dose reduction, or treatment discontinuation. CONCLUSION: Asciminib is a unique targeted TKI that provides clinicians with an additional third-line and beyond treatment option for adults with CP-CML regardless of mutation status as well as a second TKI treatment option for patients harboring a T315I mutation.
Asunto(s)
Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Adulto , Humanos , Resistencia a Antineoplásicos/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Inhibidores de Proteínas Quinasas/efectos adversos , Mutación , Antineoplásicos/efectos adversosRESUMEN
Tacrolimus is utilized as maintenance immunosuppression in solid organ transplant (SOT). Current literature has reported conflicting conversion ratios when transitioning between oral and sublingual tacrolimus, and the exact conversion ratio has not been fully established in SOT. The purpose of this study was to determine the conversion ratios between oral and sublingual tacrolimus needed to achieve equivalent whole blood concentrations in heart, kidney, liver, and lung transplant recipients. A retrospective, single-center analysis was conducted at Mayo Clinic in Florida. One hundred and eighteen hospitalized SOT recipients who received oral and sublingual tacrolimus during the same inpatient admission from June 1, 2012, through June 1, 2017, were reviewed. The median conversion ratio of sublingual to oral tacrolimus was 1.34 (IQR: 1.03-1.93) in all SOT, 1.25 (IQR: 1.08-1.64) in heart transplant, 1.23 (IQR: 1.1-2.06) in kidney transplant, 1.64 (IQR: 1.27-2.29) in liver transplant, and 1.34 (IQR: 0.94-1.93) in lung transplant. A slightly higher dose of oral tacrolimus is needed in the majority of solid organ recipients in our population when converting between sublingual to oral tacrolimus administration.