Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome - 15/09/22

Doi : 10.1016/j.jpeds.2022.05.030

Taizo A. Nakano, MD ^1,^2,^{^{∗
Contributed equally.}}, Alexander W. Rankin, MD ^2,^{^{∗
Contributed equally.}}, Aparna Annam, DO ^1,³, Ann M. Kulungowski, MD ^1,⁴, Leslie M. McCallen, MS, CGC ^1,⁵, Lauren R. Hill, CPNP-PC/AC ¹, Kathryn C. Chatfield, MD, PhD ^1,^5,^⁎
¹ Vascular Anomalies Center, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO
² Center for Cancer and Blood Disorders, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO
³ Department of Pediatric Radiology, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO
⁴ Department of Pediatric Surgery, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO
⁵ Department of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO

^∗Reprint requests: Kathryn C. Chatfield, MD, PhD, Associate Professor, Pediatrics, Pediatric Cardiology/Clinical Genetics, Children's Hospital Colorado, 13123 East 16th Avenue, B100, Aurora, CO 80045.Pediatrics, Pediatric Cardiology/Clinical GeneticsChildren's Hospital Colorado13123 East 16th Avenue, B100AuroraCO80045

Abstract

Objective

To evaluate the effect of the RAS-MAPK pathway inhibitor trametinib on medically refractory chylous effusions in 3 hospitalized patients with Noonan syndrome.

Study design

Pharmacologic MEK1/2 inhibition has been used to treat conditions associated with Noonan syndrome, given that activation of RAS-MAPK pathway variants leads to downstream MEK activation. We describe our experience with 3 patients with Noonan syndrome (owing to variants in 3 distinct genes) and refractory chylous effusions treated successfully with MEK inhibition. A monitoring protocol was established to standardize medication dosing and monitoring of outcome measures.

Results

Subjects demonstrated improvement in lymphatic leak with additional findings of improved growth and normalization of cardiac and hematologic measurements. Trametinib was administered safely, with only moderate skin irritation in 1 subject.

Conclusions

Improvements in a variety of quantifiable measurements highlight the potential utility of MEK1/2 inhibition in patients with Noonan syndrome and life-threatening lymphatic disease. Larger, prospective studies are needed to confirm efficacy and assess long-term safety.

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Keywords : Noonan syndrome, chylous effusion, chylous ascites, MEK inhibition, case series

Abbreviations : CCLA, DC-MRL, FDA, JMML, LV, NT-proBNP, sIND, WBC

Plan

T.A.N. has consulted for Novartis Pharmaceuticals to produce educational and consensus protocols unrelated to subject or products reported in this article. The other authors declare no conflicts of interest.

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Vol 248

P. 81 - septembre 2022 Retour au numéro

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Trametinib for Refractory Chylous Effusions and Systemic Complications in Children with Noonan Syndrome - 15/09/22

Abstract

Objective

Study design

Results

Conclusions

Plan

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