17 / The type of BCR/ABL1 fusion transcript does not affect therapy effectiveness of Ph-positive acute lymphocytic leukemia in the era of tyrosine kinase inhibitors in Russian trial Ph+ALL

Author(s):  
Gavrilina Olga
Blood ◽  
2021 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C Byrd

Bruton's tyrosine kinase inhibitors (BTKi) have significantly changed the treatment landscape for patients with B-cell malignancies including chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia (WM), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Unfortunately, patients with BTKi resistant disease have shortened survival. Clinical and molecular risk factors, such as number of prior therapies and presence of TP53 mutations, can be used to predict patients at the highest risk of developing BTKi resistance. Many mechanisms of BTKi resistance have been reported with mutations in BTK and phospholipase C g 2 supported with the most data. The introduction of venetoclax has lengthened the survival of patients with BTKi resistant disease. Ongoing clinical trials with promising treatment modalities such as next-generation BTKi and chimeric antigen receptor T-cell therapy have reported promising efficacy in patients with BTKi resistant disease. Continued research focusing on resistance mechanisms and methods of how to circumvent resistance is needed to further prolong the survival of patients with BTKi resistant B-cell malignancies.


2021 ◽  
pp. 225-238
Author(s):  
Sandeep Arora ◽  
Tapan Behl ◽  
Sukhbir Singh ◽  
Neelam Sharma ◽  
Nidhi Garg

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4353-4358 ◽  
Author(s):  
Dushyant Verma ◽  
Hagop Kantarjian ◽  
Sara S. Strom ◽  
Mary Beth Rios ◽  
Elias Jabbour ◽  
...  

Abstract Success of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has given patients hope for a long disease-free-survival. A longer survival raises the question of late effects, including development of another malignancy. Records of 1445 patients with CML/myeloproliferative neoplasm or other hematologic malignancies treated with TKIs were reviewed to investigate frequency and characteristics of second malignancies (other than acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndrome). The number of second cancers was compared with the number expected from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 107 months (range, 13-362 months) after CML/myeloproliferative neoplasm diagnosis, 66 patients (4.6%) developed 80 second cancers, including skin (31%), prostate (15%), melanoma (13%), digestive system (10%), kidney (4%), thyroid (4%), breast (3%), chronic lymphocytic leukemia (3%), hepatobiliary (3%), and other cancers (14%). Excluding nonmelanoma skin cancers, 55 second cancers were seen in 51 (3.5%) of all patients treated. The risk of second cancer was lower than expected (observed-to-expected ratio, 0.6; 95% confidence interval, 0.44-0.81). Second cancers occur in a small percentage of patients receiving therapy with TKIs for hematologic malignancies, mostly CML. No evidence at the moment suggests that exposure to TKIs increases the risk of developing second cancers.


Sign in / Sign up

Export Citation Format

Share Document