Customized or randomized trials for relapsed refractory pediatric Burkitt lymphomas? A retrospective analysis of two clinical cases with comprehensive molecular profiling: Possible explanation for different treatment outcomes after similar targeted therapies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F18%3A00069596" target="_blank" >RIV/65269705:_____/18:00069596 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0923753419323312" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0923753419323312</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/annonc/mdy314.037" target="_blank" >10.1093/annonc/mdy314.037</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Customized or randomized trials for relapsed refractory pediatric Burkitt lymphomas? A retrospective analysis of two clinical cases with comprehensive molecular profiling: Possible explanation for different treatment outcomes after similar targeted therapies

Popis výsledku v původním jazyce

Background: Current standard chemoimmunotherapy achieves survival in almost 95% children with mature B-NHL. However, children with relapses still carry very poor prognosis. Methods: Molecular profiling consisted of whole exome NGS, gene expression profiling and peripheral blood phosphoflow. Results: Both cases had identical clinical presentation and histology, progressed early during standard therapy and did not respond to intensive retrieval chemotherapy. In the first patient, a germ line variant of c.935C&gt;G in the PI3K-delta subunit was found. Activation of PI3K downstream signaling pathway was detected using flow cytometry in patient&apos;s peripheral blood lymphocytes. Increased levels of PI3K were confirmed also by gene expression profiling together with an increased expression of HR23B. Immunohistochemistry revealed strong expression of PD-1L. Therapy was changed to a single agent idelalisib window. In two weeks there was markedly decreased PI3K pathway activation in patient&apos;s lymphocytes, but the disease still showed a radiological progression. During the time, ibrutinib, valproic acid, nivolumab and metronomic cyclophosphamide was added and local 21Gy radiation to the site of the abdominal relapse was used. Partial remission was documented and personalized immunotherapy with autologous dendritic cell-based vaccine was given. Residual tumor resected after 11 months did not show any viable tumor and treatment was gradually tapered down. His 3rd EFS 31 months on personalized treatment is the longest he ever experienced. The second patient died 11 months form diagnosis. Conclusions: The first case was successfully treated with targeted and immune therapy that matched the molecular signature of the tumor, but in the second case, the therapy &quot;missed&quot; the target, because his molecular signature was not known at the time retrieval therapy. The findings suggest that molecular signatures among clinically and histologically similar patients could be unique, and a tissue biomarker-based customized therapy may be the best approach to address these poor prognosis patients.

Název v anglickém jazyce

Customized or randomized trials for relapsed refractory pediatric Burkitt lymphomas? A retrospective analysis of two clinical cases with comprehensive molecular profiling: Possible explanation for different treatment outcomes after similar targeted therapies

Popis výsledku anglicky

Background: Current standard chemoimmunotherapy achieves survival in almost 95% children with mature B-NHL. However, children with relapses still carry very poor prognosis. Methods: Molecular profiling consisted of whole exome NGS, gene expression profiling and peripheral blood phosphoflow. Results: Both cases had identical clinical presentation and histology, progressed early during standard therapy and did not respond to intensive retrieval chemotherapy. In the first patient, a germ line variant of c.935C&gt;G in the PI3K-delta subunit was found. Activation of PI3K downstream signaling pathway was detected using flow cytometry in patient&apos;s peripheral blood lymphocytes. Increased levels of PI3K were confirmed also by gene expression profiling together with an increased expression of HR23B. Immunohistochemistry revealed strong expression of PD-1L. Therapy was changed to a single agent idelalisib window. In two weeks there was markedly decreased PI3K pathway activation in patient&apos;s lymphocytes, but the disease still showed a radiological progression. During the time, ibrutinib, valproic acid, nivolumab and metronomic cyclophosphamide was added and local 21Gy radiation to the site of the abdominal relapse was used. Partial remission was documented and personalized immunotherapy with autologous dendritic cell-based vaccine was given. Residual tumor resected after 11 months did not show any viable tumor and treatment was gradually tapered down. His 3rd EFS 31 months on personalized treatment is the longest he ever experienced. The second patient died 11 months form diagnosis. Conclusions: The first case was successfully treated with targeted and immune therapy that matched the molecular signature of the tumor, but in the second case, the therapy &quot;missed&quot; the target, because his molecular signature was not known at the time retrieval therapy. The findings suggest that molecular signatures among clinically and histologically similar patients could be unique, and a tissue biomarker-based customized therapy may be the best approach to address these poor prognosis patients.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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