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Wyświetlanie 1-10 z 11
Tytuł:
Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richters transformation
Autorzy:
Hodkinson, Brendan P.
Avivi, Irit
Brody, Joshua D.
Schaffer, Michael
Alvarez, John
Ceulemans, Rob
Fourneau, Nele
Ben-Yehuda, Dina
Forslund, Ann
Younes, Anas
Balasubramanian, Sriram
Jurczak, Wojciech
Carpio, Cecilia
Opis:
We analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter's transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5%] vs. 3/16 [18.8%]; p = 0.065; complete response 37.5% vs. 0%; p = 0.028). Overall response rates for patients with WES and GEP data, respectively, were: DLBCL (38.5% and 29.6%); FL (46.2% and 43.5%); RT (76.5% and 81.3%). In DLBCL, WES analyses demonstrated that mutations in RNF213 (40.0% vs. 6.2%; p = 0.055), KLHL14 (30.0% vs. 0%; p = 0.046), and LRP1B (30.0% vs. 6.2%; p = 0.264) were more frequent in responders. No responders had mutations in EBF1, ADAMTS20, AKAP9, TP53, MYD88, or TNFRSF14, while the frequency of these mutations in nonresponders ranged from 12.5% to 18.8%. In FL and RT, genes with different mutation frequencies in responders versus nonresponders were: BCL2 (75.0% vs. 28.6%; p = 0.047) and ROS1 (0% vs. 50.0%; p = 0.044), respectively. Per GEP, the most upregulated genes in responders were LEF1 and BTLA (overall), and CRTAM (germinal center B-cell–like DLBCL). Enriched pathways were related to immune activation in responders and resistance-associated proliferation/replication in nonresponders. This preliminary work may help to generate hypotheses regarding genetically defined subsets of DLBCL, FL, and RT patients most likely to benefit from ibrutinib plus nivolumab.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Outcome of second primary malignancies developing in multiple myeloma patients
Autorzy:
Weisel, Katja
Kopińska, Anna
Crusoe, Edvan
Puertas-Martinez, Borja
Rodriguez-Lobato, Luis Gerardo
Waszczuk-Gajda, Anna
Krzystański, Mateusz
Osękowska, Bogumiła
Vesole, David H.
Davila-Valls, Julio
Shustik, Chaim
Mikala, Gabor
Robak, Paweł
Alexander, H. Denis
Gozzetti, Alessandro
Barth, Peter
Avivi, Irit
Milunovic, Vibor
Zalac, Klara
Varga, Gergely
Usnarska-Zubkiewicz, Lidia
Gajewska, Małgorzata
Baumert, Bartłomiej
Pena, Camila
Gentile, Massimo
Martinez-Lopez, Joaquin
Cohen, Yael
Jurczyszyn, Artur
Olszewska-Szopa, Magdalena
Delforge, Michel
Opis:
Background: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational ‘real-world’ retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs. Results: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger (p = 0.05) and more frequently had a prior AutoHCT (p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32–14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19–0.95, p = 0.037) predicted longer OS. Conclusions: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Wyświetlanie 1-10 z 11

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