Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10400190" target="_blank" >RIV/00064203:_____/19:10400190 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/19:10400190

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=4qwvzWlZwW" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=4qwvzWlZwW</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1200/JCO.19.00456" target="_blank" >10.1200/JCO.19.00456</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study

Popis výsledku v původním jazyce

PURPOSE: Off-label use of vemurafenib (VMF) to treat BRAFV600E mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. PATIENTS AND METHODS: Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score. RESULTS: LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 (P &lt; .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAFV600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P &lt; .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAFV600E clone. CONCLUSION: VMF seemed safe and effective in children with refractory BRAFV600E-positive LCH. Additional studies are needed to find effective maintenance therapy approaches.

Název v anglickém jazyce

Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study

Popis výsledku anglicky

PURPOSE: Off-label use of vemurafenib (VMF) to treat BRAFV600E mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. PATIENTS AND METHODS: Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score. RESULTS: LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 (P &lt; .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAFV600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P &lt; .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAFV600E clone. CONCLUSION: VMF seemed safe and effective in children with refractory BRAFV600E-positive LCH. Additional studies are needed to find effective maintenance therapy approaches.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Clinical Oncology

ISSN

0732-183X

e-ISSN

—

Svazek periodika

37

Číslo periodika v rámci svazku

31

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

2857-2865

Kód UT WoS článku

000501780200006

EID výsledku v databázi Scopus

2-s2.0-85074307588